Contact
Biomedical Research Center251 Bayview Boulevard
Baltimore, MD 21224
Email: juan.gomez@nih.gov
Education
B.S. - Psychology, Arizona State University
Ph.D. - Hunter College
Background
A statement about my-[science]-self: I have a curiosity driven by the need to explore; doing my best to improve upon methods and techniques to devise a better way to catch that roadrunner.
Thoughts on experience: High School – An introduction to the lab, samples, and 96-wells. As a junior, I volunteered my school breaks and weekends to assist a biology graduate collecting and analyzing water/soil samples from rivers in Arizona. I was one of the few high school students among undergraduates to present our findings at the annual Arizona State University poster day. I was hooked. Undergraduate (B.S.) – An undergrad is only an undergrad by name in the lab of Cheryl Conrad at Arizona State University (ASU) where I received a degree in Psychology. These early experiences sharpened my lab work ethic and expectations as a future academic. Graduate (Ph.D.) – Good work with those that work good with you. Mentored by Victoria Luine, we worked with Michael Lewis and others at Hunter College of CUNY (HC) on my dissertation. Collaborations were an integral part of my graduate career, and almost every lab at HC contributed to my development as a scientist, for which I am grateful. Postdoc #1 – Envy has no place in productive endeavors. At my first postdoc in the Behavioral Neuroscience department at Oregon Health & Science University (OHSU), I was exposed to a new level of research and opportunities. Working with Andrey Ryabinin I learned the value of independent research and perseverance during difficult times. Postdoc #2 – Further research is needed… I joined the BIMN lab in 2015. Thus far, the radioactive signal may show me the way.
Research Interests
Dr. Juan Gomez is a Postdoctoral Fellow at the National Institute on Drug Abuse (NIDA) in Baltimore, Maryland. In August 2015 he was the first member hired for the newly established Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit headed by Dr. Michael Michaelides. He joined NIDA from Oregon Health and Science University after a brief postdoc with Dr. Andrey Ryabinin where he explored the role of the neuropeptide ghrelin in rodent models of alcohol dependence. His doctoral research was conducted with Dr. Victoria Luine at Hunter College, where he studied interactions between alcohol exposure and stress in rodents and received his Ph.D. from The Graduate Center of CUNY in 2012. Prior to this he was an undergraduate research fellow with Dr. Cheryl Conrad at Arizona State University investigating the effects of chronic stress on spatial memory and hippocampal morphology and received his B.S. in 2006.
At NIDA, Dr. Gomez helped design and set up a new laboratory space integrating PET imaging and behavioral neuroscience modalities. His training has involved both formal courses in small animal in vivo imaging and in PET pharmacokinetic analyses along with laboratory training at NIDA which has combined cutting-edge neuromodulation technologies with noninvasive imaging (PET) in rodents and in nonhuman primates. Dr. Gomez has published first-authored articles in various journals including his most recent publication in Science involving the precise characterization of the mechanism of action of DREADD neuromodulation technology. His more recent work involves studying brain zinc and its contribution to substance abuse vulnerability and PET imaging methods for visualizing novel neuromodulation technologies.
Publications
Selected Publications
2017
Gomez, Juan L; Bonaventura, Jordi; Lesniak, Wojciech; Mathews, William B; Sysa-Shah, Polina; Rodriguez, Lionel A; Ellis, Randall J; Richie, Christopher T; Harvey, Brandon K; Dannals, Robert F; Pomper, Martin G; Bonci, Antonello; Michaelides, Michael
Chemogenetics revealed: DREADD occupancy and activation via converted clozapine. Journal Article
In: Science, vol. 357, no. 6350, pp. 503–507, 2017, ISSN: 1095-9203 (Electronic); 0036-8075 (Linking).
@article{Gomez2017,
title = {Chemogenetics revealed: DREADD occupancy and activation via converted clozapine.},
author = {Juan L Gomez and Jordi Bonaventura and Wojciech Lesniak and William B Mathews and Polina Sysa-Shah and Lionel A Rodriguez and Randall J Ellis and Christopher T Richie and Brandon K Harvey and Robert F Dannals and Martin G Pomper and Antonello Bonci and Michael Michaelides},
url = {https://www.ncbi.nlm.nih.gov/pubmed/28774929},
doi = {10.1126/science.aan2475},
issn = {1095-9203 (Electronic); 0036-8075 (Linking)},
year = {2017},
date = {2017-08-04},
urldate = {2017-08-04},
journal = {Science},
volume = {357},
number = {6350},
pages = {503--507},
address = {Biobehavioral Imaging and Molecular Neuropsychopharmacology Unit, National Institute on Drug Abuse (NIDA) Intramural Research Program, Baltimore, MD 21224, USA.},
abstract = {The chemogenetic technology DREADD (designer receptors exclusively activated by designer drugs) is widely used for remote manipulation of neuronal activity in freely moving animals. DREADD technology posits the use of "designer receptors," which are exclusively activated by the "designer drug" clozapine N-oxide (CNO). Nevertheless, the in vivo mechanism of action of CNO at DREADDs has never been confirmed. CNO does not enter the brain after systemic drug injections and shows low affinity for DREADDs. Clozapine, to which CNO rapidly converts in vivo, shows high DREADD affinity and potency. Upon systemic CNO injections, converted clozapine readily enters the brain and occupies central nervous system-expressed DREADDs, whereas systemic subthreshold clozapine injections induce preferential DREADD-mediated behaviors.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The chemogenetic technology DREADD (designer receptors exclusively activated by designer drugs) is widely used for remote manipulation of neuronal activity in freely moving animals. DREADD technology posits the use of "designer receptors," which are exclusively activated by the "designer drug" clozapine N-oxide (CNO). Nevertheless, the in vivo mechanism of action of CNO at DREADDs has never been confirmed. CNO does not enter the brain after systemic drug injections and shows low affinity for DREADDs. Clozapine, to which CNO rapidly converts in vivo, shows high DREADD affinity and potency. Upon systemic CNO injections, converted clozapine readily enters the brain and occupies central nervous system-expressed DREADDs, whereas systemic subthreshold clozapine injections induce preferential DREADD-mediated behaviors.
2016
Luine, Victoria; Gomez, Juan; Beck, Kevin; Bowman, Rachel
Sex differences in chronic stress effects on cognition in rodents. Journal Article
In: Pharmacol Biochem Behav, vol. 152, pp. 13–19, 2016, ISSN: 1873-5177 (Electronic); 0091-3057 (Linking).
@article{Luine2016,
title = {Sex differences in chronic stress effects on cognition in rodents.},
author = {Victoria Luine and Juan Gomez and Kevin Beck and Rachel Bowman},
url = {https://www.ncbi.nlm.nih.gov/pubmed/27566290},
doi = {10.1016/j.pbb.2016.08.005},
issn = {1873-5177 (Electronic); 0091-3057 (Linking)},
year = {2016},
date = {2016-08-24},
journal = {Pharmacol Biochem Behav},
volume = {152},
pages = {13--19},
address = {Department of Psychology, Hunter College of CUNY, New York, NY 10065, United States. Electronic address: vluine@hunter.cuny.edu.},
abstract = {Chronic stress causes deleterious changes in physiological function in systems ranging from neural cells in culture to laboratory rodents, sub-human primates and humans. It is notable, however, that the vast majority of research in this area has been conducted in males. In this review, we provide information about chronic stress effects on cognition in female rodents and contrast it with responses in male rodents. In general, females show cognitive resilience to chronic stressors which impair male cognitive function using spatial tasks including the radial arm maze, radial arm water maze, Morris water maze, Y-maze and object placement. Moreover, stress often enhances female performance in some of these cognitive tasks. Memory in females is not affected by stress in non-spatial memory tasks like recognition memory and temporal order recognition memory while males show impaired memory following stress. We discuss possible bases for these sex-dependent differences including the use of different strategies by the sexes to solve cognitive tasks. Whether the sex differences result from changes in non-mnemonic factors is also considered. Sex-dependent differences in alcohol and drug influences on stress responses are also described. Finally, the role of neurally derived estradiol in driving sex differences and providing resilience to stress in females is shown. The importance of determining the nature and extent of sex differences in stress responses is that such differences may provide vital information for understanding why some stress related diseases have different incidence rates between the sexes and for developing novel therapeutic treatments.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chronic stress causes deleterious changes in physiological function in systems ranging from neural cells in culture to laboratory rodents, sub-human primates and humans. It is notable, however, that the vast majority of research in this area has been conducted in males. In this review, we provide information about chronic stress effects on cognition in female rodents and contrast it with responses in male rodents. In general, females show cognitive resilience to chronic stressors which impair male cognitive function using spatial tasks including the radial arm maze, radial arm water maze, Morris water maze, Y-maze and object placement. Moreover, stress often enhances female performance in some of these cognitive tasks. Memory in females is not affected by stress in non-spatial memory tasks like recognition memory and temporal order recognition memory while males show impaired memory following stress. We discuss possible bases for these sex-dependent differences including the use of different strategies by the sexes to solve cognitive tasks. Whether the sex differences result from changes in non-mnemonic factors is also considered. Sex-dependent differences in alcohol and drug influences on stress responses are also described. Finally, the role of neurally derived estradiol in driving sex differences and providing resilience to stress in females is shown. The importance of determining the nature and extent of sex differences in stress responses is that such differences may provide vital information for understanding why some stress related diseases have different incidence rates between the sexes and for developing novel therapeutic treatments.
2015
Gomez, Juan L; Cunningham, Christopher L; Finn, Deborah A; Young, Emily A; Helpenstell, Lily K; Schuette, Lindsey M; Fidler, Tara L; Kosten, Therese A; Ryabinin, Andrey E
Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence. Journal Article
In: Neuropharmacology, vol. 97, pp. 182–193, 2015, ISSN: 1873-7064 (Electronic); 0028-3908 (Linking).
@article{Gomez2015,
title = {Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence.},
author = {Juan L Gomez and Christopher L Cunningham and Deborah A Finn and Emily A Young and Lily K Helpenstell and Lindsey M Schuette and Tara L Fidler and Therese A Kosten and Andrey E Ryabinin},
url = {https://www.ncbi.nlm.nih.gov/pubmed/26051399},
doi = {10.1016/j.neuropharm.2015.05.026},
issn = {1873-7064 (Electronic); 0028-3908 (Linking)},
year = {2015},
date = {2015-06-04},
journal = {Neuropharmacology},
volume = {97},
pages = {182--193},
address = {Oregon Health & Science University, Department of Behavioral Neuroscience and Portland Alcohol Research Center, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA. Electronic address: GomezJ@ohsu.edu.},
abstract = {An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increase alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects of ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
An effort has been mounted to understand the mechanisms of alcohol dependence in a way that may allow for greater efficacy in treatment. It has long been suggested that drugs of abuse seize fundamental reward pathways and disrupt homeostasis to produce compulsive drug seeking behaviors. Ghrelin, an endogenous hormone that affects hunger state and release of growth hormone, has been shown to increase alcohol intake following administration, while antagonists decrease intake. Using rodent models of dependence, the current study examined the effects of two ghrelin receptor antagonists, [DLys3]-GHRP-6 (DLys) and JMV2959, on dependence-induced alcohol self-administration. In two experiments adult male C57BL/6J mice and Wistar rats were made dependent via intermittent ethanol vapor exposure. In another experiment, adult male C57BL/6J mice were made dependent using the intragastric alcohol consumption (IGAC) procedure. Ghrelin receptor antagonists were given prior to voluntary ethanol drinking. Ghrelin antagonists reduced ethanol intake, preference, and operant self-administration of ethanol and sucrose across these models, but did not decrease food consumption in mice. In experiments 1 and 2, voluntary drinking was reduced by ghrelin receptor antagonists, however this reduction did not persist across days. Despite the transient effects of ghrelin antagonists, the drugs had renewed effectiveness following a break in administration as seen in experiment 1. The results show the ghrelin system as a potential target for studies of alcohol abuse. Further research is needed to determine the central mechanisms of these drugs and their influence on addiction in order to design effective pharmacotherapies.
2014
Gomez, Juan L; Ryabinin, Andrey E
The effects of ghrelin antagonists [D-Lys(3)]-GHRP-6 or JMV2959 on ethanol, water, and food intake in C57BL/6J mice. Journal Article
In: Alcohol Clin Exp Res, vol. 38, no. 9, pp. 2436–2444, 2014, ISSN: 1530-0277 (Electronic); 0145-6008 (Linking).
@article{Gomez2014,
title = {The effects of ghrelin antagonists [D-Lys(3)]-GHRP-6 or JMV2959 on ethanol, water, and food intake in C57BL/6J mice.},
author = {Juan L Gomez and Andrey E Ryabinin},
url = {https://www.ncbi.nlm.nih.gov/pubmed/25257292},
doi = {10.1111/acer.12499},
issn = {1530-0277 (Electronic); 0145-6008 (Linking)},
year = {2014},
date = {2014-09-01},
journal = {Alcohol Clin Exp Res},
volume = {38},
number = {9},
pages = {2436--2444},
address = {Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, Oregon.},
abstract = {BACKGROUND: Alcohol use and abuse patterns have created a need for novel treatment models. Current research has turned its focus on reward pathways associated with intrinsic necessities, such as feeding. Theories suggest that drugs of abuse seize control of natural reward pathways and dysregulate normal function, leading to chronic addiction. One such pathway involving the hunger stimulating peptide, ghrelin, is the focus of our study. METHODS: Male C57BL/6J mice were randomly assigned to groups and treated with vehicle or a ghrelin antagonist, either [D-Lys(3) ]-GHRP-6 (DLys) or JMV2959. Three experiments tested ghrelin antagonism using different doses; experiment 1 tested 12 mg/kg JMV2959; experiment 2 tested 15 mg/kg DLys; experiment 3 tested 9 mg/kg JMV2959. Using a 2-bottle choice 24-hour access paradigm, data were collected for ethanol intake, preference, water intake, and food intake at 4 and 24 hours after injection. RESULTS: Experiment 1 showed that 12 mg/kg of JMV2959 decreased ethanol, water, and food intake, without affecting preference. Experiment 2 showed that 15 mg/kg of DLys decreased ethanol intake, preference, and water intake only on the first day of treatment. Experiment 3 showed that 9 mg/kg of JMV2959 decreased only ethanol and food intake. No change was seen during deprivation, and JMV2959 was still effective at reducing ethanol intake upon reintroduction. Despite the change in food intake, there were no differences in body weight throughout the experiments. It should be noted that the majority of significant effects were only found 4 hours postinjection. CONCLUSIONS: The results show that compounds that block ghrelin receptor activity are effective at decreasing ethanol intake. However, DLys was only effective at reducing intake and preference on the first day, suggesting a quick tolerance and selectivity for ethanol. JMV2959 consistently reduced ethanol intake, but at the higher dose also reduced all other consummatory behaviors. Thus, ghrelin antagonists provide a viable potential for treatment of alcohol abuse disorders, but further research is needed to determine an appropriate dose and administration paradigm.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
BACKGROUND: Alcohol use and abuse patterns have created a need for novel treatment models. Current research has turned its focus on reward pathways associated with intrinsic necessities, such as feeding. Theories suggest that drugs of abuse seize control of natural reward pathways and dysregulate normal function, leading to chronic addiction. One such pathway involving the hunger stimulating peptide, ghrelin, is the focus of our study. METHODS: Male C57BL/6J mice were randomly assigned to groups and treated with vehicle or a ghrelin antagonist, either [D-Lys(3) ]-GHRP-6 (DLys) or JMV2959. Three experiments tested ghrelin antagonism using different doses; experiment 1 tested 12 mg/kg JMV2959; experiment 2 tested 15 mg/kg DLys; experiment 3 tested 9 mg/kg JMV2959. Using a 2-bottle choice 24-hour access paradigm, data were collected for ethanol intake, preference, water intake, and food intake at 4 and 24 hours after injection. RESULTS: Experiment 1 showed that 12 mg/kg of JMV2959 decreased ethanol, water, and food intake, without affecting preference. Experiment 2 showed that 15 mg/kg of DLys decreased ethanol intake, preference, and water intake only on the first day of treatment. Experiment 3 showed that 9 mg/kg of JMV2959 decreased only ethanol and food intake. No change was seen during deprivation, and JMV2959 was still effective at reducing ethanol intake upon reintroduction. Despite the change in food intake, there were no differences in body weight throughout the experiments. It should be noted that the majority of significant effects were only found 4 hours postinjection. CONCLUSIONS: The results show that compounds that block ghrelin receptor activity are effective at decreasing ethanol intake. However, DLys was only effective at reducing intake and preference on the first day, suggesting a quick tolerance and selectivity for ethanol. JMV2959 consistently reduced ethanol intake, but at the higher dose also reduced all other consummatory behaviors. Thus, ghrelin antagonists provide a viable potential for treatment of alcohol abuse disorders, but further research is needed to determine an appropriate dose and administration paradigm.
2013
Gomez, J L; Luine, V N
Female rats exposed to stress and alcohol show impaired memory and increased depressive-like behaviors. Journal Article
In: Physiol Behav, vol. 123, pp. 47–54, 2013, ISSN: 1873-507X (Electronic); 0031-9384 (Linking).
@article{Gomez2013,
title = {Female rats exposed to stress and alcohol show impaired memory and increased depressive-like behaviors.},
author = {J L Gomez and V N Luine},
url = {https://www.ncbi.nlm.nih.gov/pubmed/24096191},
doi = {10.1016/j.physbeh.2013.09.009},
issn = {1873-507X (Electronic); 0031-9384 (Linking)},
year = {2013},
date = {2013-10-01},
journal = {Physiol Behav},
volume = {123},
pages = {47--54},
address = {Department of Psychology, Hunter College of CUNY, 695 Park Ave, New York, NY 10065, USA; Department of Psychology, The Graduate Center of CUNY, 365 Fifth Ave, New York, NY 10016, USA. Electronic address: GomezJ@ohsu.edu.},
abstract = {Exposure to daily life stressors is associated with increases in anxiety, depression, and overall negative affect. Alcohol or other psychoactive drugs are often used to alleviate stress effects. While females are more than twice as likely to develop mood disorders and are more susceptible to dependency than males, they are infrequently examined. In this study, female rats received no stress/no alcohol control (CON), alcohol alone (ALC), stress alone (STR), or stress plus alcohol (STR+ALC). Stress consisted of restraint for 6h/day/7days, and alcohol was administered immediately following restraint via gastric gavage at a dose of 2.0g/kg. Dependent measures included tests utilizing object recognition (OR), Y-maze, elevated plus maze (EPM), forced swim (FST), blood alcohol content, corticosterone levels, and body weights. ALC, STR+ALC, but not stress alone, impaired memory on OR. All treatments impaired spatial memory on the Y-maze. Anxiety was not affected on the EPM, but rats treated with alcohol or in combination with stress showed increased immobility on the FST, suggestive of alcohol-induced depression. Previously, we found alcohol reversed deleterious effects of stress on memory and mood in males, but current results show that females reacted negatively when the two treatments were combined. Thus, responses to alcohol, stress and their combination suggest that sex specific treatments are needed for stress-induced behavioral changes and that self-medicating with alcohol to cope with stress maybe deleterious in females.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Exposure to daily life stressors is associated with increases in anxiety, depression, and overall negative affect. Alcohol or other psychoactive drugs are often used to alleviate stress effects. While females are more than twice as likely to develop mood disorders and are more susceptible to dependency than males, they are infrequently examined. In this study, female rats received no stress/no alcohol control (CON), alcohol alone (ALC), stress alone (STR), or stress plus alcohol (STR+ALC). Stress consisted of restraint for 6h/day/7days, and alcohol was administered immediately following restraint via gastric gavage at a dose of 2.0g/kg. Dependent measures included tests utilizing object recognition (OR), Y-maze, elevated plus maze (EPM), forced swim (FST), blood alcohol content, corticosterone levels, and body weights. ALC, STR+ALC, but not stress alone, impaired memory on OR. All treatments impaired spatial memory on the Y-maze. Anxiety was not affected on the EPM, but rats treated with alcohol or in combination with stress showed increased immobility on the FST, suggestive of alcohol-induced depression. Previously, we found alcohol reversed deleterious effects of stress on memory and mood in males, but current results show that females reacted negatively when the two treatments were combined. Thus, responses to alcohol, stress and their combination suggest that sex specific treatments are needed for stress-induced behavioral changes and that self-medicating with alcohol to cope with stress maybe deleterious in females.
Gomez, J L; Lewis, M J; Sebastian, V; Serrano, P; Luine, V N
In: Horm Behav, vol. 63, no. 4, pp. 659–666, 2013, ISSN: 1095-6867 (Electronic); 0018-506X (Linking).
@article{Gomez2013b,
title = {Alcohol administration blocks stress-induced impairments in memory and anxiety, and alters hippocampal neurotransmitter receptor expression in male rats.},
author = {J L Gomez and M J Lewis and V Sebastian and P Serrano and V N Luine},
url = {https://www.ncbi.nlm.nih.gov/pubmed/23376488},
doi = {10.1016/j.yhbeh.2013.01.007},
issn = {1095-6867 (Electronic); 0018-506X (Linking)},
year = {2013},
date = {2013-02-01},
journal = {Horm Behav},
volume = {63},
number = {4},
pages = {659--666},
address = {Department of Psychology, Hunter College of CUNY, 695 Park Ave, New York, NY 10065, USA. Juan.Gomez@hunter.cuny.edu},
abstract = {Chronic exposure to stress has many deleterious effects on behavior, which can often lead to self-medication with anxiolytics, antidepressants, or alcohol. We determined the effects of alcohol administration following a stressor on established behavioral, physiological, and neural responses to stress. Male Sprague-Dawley rats received: No alcohol/No stress (CON), Alcohol alone (ALC), Stress alone (STR), or Stress plus Alcohol (STR+ALC). For seven consecutive days, two cohorts received an oral dose of 2.0 g/kg of either 20% ethanol or saline. In Cohort 1, behavioral testing began after the final treatment (day-8). Memory was tested using the object recognition (OR) and Y-maze, anxiety on the plus maze, and depression on the forced swim task. Memory on OR and Y-maze tasks was impaired in the ALC and STR groups. This deficit was reversed in the STR+ALC group, which performed not differently from the CON group. Stress alone was associated with increased anxiety, which was alleviated with alcohol treatment. No treatment effects were found in the forced swim task. In Cohort 2, hippocampal GABAalpha4 was upregulated in the STR+ALC group and GluN2B was upregulated in the ALC and STR+ALC groups. The STR+ALC group in Cohort 1 showed enhanced corticosterone levels after forced swim. The STR+ALC group in Cohort 2 showed increased corticosterone levels on day-1 of treatment and a habituation by day-7. In conclusion, this study found a reversal of stress-induced deficits in cognition and anxiety when alcohol was given post-stress, and changes in neurotransmitter receptor expression may contribute to these behavioral effects.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chronic exposure to stress has many deleterious effects on behavior, which can often lead to self-medication with anxiolytics, antidepressants, or alcohol. We determined the effects of alcohol administration following a stressor on established behavioral, physiological, and neural responses to stress. Male Sprague-Dawley rats received: No alcohol/No stress (CON), Alcohol alone (ALC), Stress alone (STR), or Stress plus Alcohol (STR+ALC). For seven consecutive days, two cohorts received an oral dose of 2.0 g/kg of either 20% ethanol or saline. In Cohort 1, behavioral testing began after the final treatment (day-8). Memory was tested using the object recognition (OR) and Y-maze, anxiety on the plus maze, and depression on the forced swim task. Memory on OR and Y-maze tasks was impaired in the ALC and STR groups. This deficit was reversed in the STR+ALC group, which performed not differently from the CON group. Stress alone was associated with increased anxiety, which was alleviated with alcohol treatment. No treatment effects were found in the forced swim task. In Cohort 2, hippocampal GABAalpha4 was upregulated in the STR+ALC group and GluN2B was upregulated in the ALC and STR+ALC groups. The STR+ALC group in Cohort 1 showed enhanced corticosterone levels after forced swim. The STR+ALC group in Cohort 2 showed increased corticosterone levels on day-1 of treatment and a habituation by day-7. In conclusion, this study found a reversal of stress-induced deficits in cognition and anxiety when alcohol was given post-stress, and changes in neurotransmitter receptor expression may contribute to these behavioral effects.
2012
Gomez, Juan L; Lewis, Michael J; Luine, Victoria N
The interaction of chronic restraint stress and voluntary alcohol intake: effects on spatial memory in male rats. Journal Article
In: Alcohol, vol. 46, no. 5, pp. 499–504, 2012, ISSN: 1873-6823 (Electronic); 0741-8329 (Linking).
@article{Gomez2012,
title = {The interaction of chronic restraint stress and voluntary alcohol intake: effects on spatial memory in male rats.},
author = {Juan L Gomez and Michael J Lewis and Victoria N Luine},
url = {https://www.ncbi.nlm.nih.gov/pubmed/22560292},
doi = {10.1016/j.alcohol.2011.12.005},
issn = {1873-6823 (Electronic); 0741-8329 (Linking)},
year = {2012},
date = {2012-05-02},
journal = {Alcohol},
volume = {46},
number = {5},
pages = {499--504},
address = {Doctoral Program in Biopsychology and Behavioral Neuroscience, The Graduate Center of City University of New York (CUNY), New York, NY 10016, USA. Juan.Gomez@hunter.cuny.edu},
abstract = {Alcohol consumption and exposure to stressful life events activate similar neural pathways and thus result in several comparable physiological and behavioral effects. Alcoholics in treatment claim that life stressors are the leading cause of continued drinking or relapse. However, few studies have investigated the interactive effects of stress and alcohol on cognitive behavior. The effects of restraint stress, alcohol, and stress in combination with alcohol were examined on a spatial memory test, the object placement (OP) task. In addition, intake levels were measured to determine if stress altered general consumption of alcohol. Male Sprague-Dawley rats were assigned to one of four conditions: no alcohol/no stress control (CON), stress alone (STR), alcohol alone (ALC), and STR+alcohol (STR+ALC). Following each restraint stress bout, the STR+ALC and the ALC groups were given access to 8% alcohol for 1h using the two-bottle choice limited access paradigm. As predicted, the STR+ALC group significantly increased alcohol consumption, while the ALC group had consistent drinking over the 10-day treatment. On the OP task, STR and ALC groups performed at chance levels, whereas the CON and STR+ALC groups significantly discriminated between objects in the new and old locations. These data show that stress increases alcohol intake and the intake of alcohol is associated with reduction of the stress-induced impairment of spatial memory. The data have important implications for the development of alcohol abuse and its treatment.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alcohol consumption and exposure to stressful life events activate similar neural pathways and thus result in several comparable physiological and behavioral effects. Alcoholics in treatment claim that life stressors are the leading cause of continued drinking or relapse. However, few studies have investigated the interactive effects of stress and alcohol on cognitive behavior. The effects of restraint stress, alcohol, and stress in combination with alcohol were examined on a spatial memory test, the object placement (OP) task. In addition, intake levels were measured to determine if stress altered general consumption of alcohol. Male Sprague-Dawley rats were assigned to one of four conditions: no alcohol/no stress control (CON), stress alone (STR), alcohol alone (ALC), and STR+alcohol (STR+ALC). Following each restraint stress bout, the STR+ALC and the ALC groups were given access to 8% alcohol for 1h using the two-bottle choice limited access paradigm. As predicted, the STR+ALC group significantly increased alcohol consumption, while the ALC group had consistent drinking over the 10-day treatment. On the OP task, STR and ALC groups performed at chance levels, whereas the CON and STR+ALC groups significantly discriminated between objects in the new and old locations. These data show that stress increases alcohol intake and the intake of alcohol is associated with reduction of the stress-induced impairment of spatial memory. The data have important implications for the development of alcohol abuse and its treatment.
2010
McLaughlin, Katie J; Wilson, Jessica O; Harman, James; Wright, Ryan L; Wieczorek, Lindsay; Gomez, Juan; Korol, Donna L; Conrad, Cheryl D
In: Hippocampus, vol. 20, no. 6, pp. 768–786, 2010, ISSN: 1098-1063 (Electronic); 1050-9631 (Linking).
@article{McLaughlin2010,
title = {Chronic 17beta-estradiol or cholesterol prevents stress-induced hippocampal CA3 dendritic retraction in ovariectomized female rats: possible correspondence between CA1 spine properties and spatial acquisition.},
author = {Katie J McLaughlin and Jessica O Wilson and James Harman and Ryan L Wright and Lindsay Wieczorek and Juan Gomez and Donna L Korol and Cheryl D Conrad},
url = {https://www.ncbi.nlm.nih.gov/pubmed/19650122},
doi = {10.1002/hipo.20678},
issn = {1098-1063 (Electronic); 1050-9631 (Linking)},
year = {2010},
date = {2010-06-01},
journal = {Hippocampus},
volume = {20},
number = {6},
pages = {768--786},
address = {Department of Psychology, Arizona State University, Tempe, Arizona 85287-1104, USA. mclaughlin@loras.edu},
abstract = {Chronic stress may have different effects on hippocampal CA3 and CA1 neuronal morphology and function depending upon hormonal status, but rarely are manipulations of stress and gonadal steroids combined. Experiment 1 investigated the effects of chronic restraint and 17beta-estradiol replacement on CA3 and CA1 dendritic morphology and spatial learning in ovariectomized (OVX) female Sprague-Dawley rats. OVX rats were implanted with 25% 17beta-estradiol, 100% cholesterol, or blank silastic capsules and then chronically restrained (6h/d/21d) or kept in home cages. 17beta-Estradiol or cholesterol prevented stress-induced CA3 dendritic retraction, increased CA1 apical spine density, and altered CA1 spine shape. The combination of chronic stress and 17beta-estradiol facilitated water maze acquisition compared to chronic stress + blank implants and nonstressed controls + 17beta-estradiol. To further investigate the interaction between 17beta-estradiol and stress on hippocampal morphology, experiment 2 was conducted on gonadally intact, cycling female rats that were chronically restrained (6h/d/21d), and then euthanized at proestrus (high ovarian hormones) or estrus (low ovarian hormones). Cycling female rats failed to show chronic stress-induced CA3 dendritic retraction at either estrous phase. Chronic stress enhanced the ratio of CA1 basal spine heads to headless spines as found in experiment 1. In addition, proestrous rats displayed increased CA1 spine density regardless of stress history. These results show that 17beta-estradiol or cholesterol protect against chronic stress-induced CA3 dendritic retraction in females. These stress- and 17beta-estradiol-induced morphological changes may provide insight into how dendritic complexity and spine properties contribute to spatial ability.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chronic stress may have different effects on hippocampal CA3 and CA1 neuronal morphology and function depending upon hormonal status, but rarely are manipulations of stress and gonadal steroids combined. Experiment 1 investigated the effects of chronic restraint and 17beta-estradiol replacement on CA3 and CA1 dendritic morphology and spatial learning in ovariectomized (OVX) female Sprague-Dawley rats. OVX rats were implanted with 25% 17beta-estradiol, 100% cholesterol, or blank silastic capsules and then chronically restrained (6h/d/21d) or kept in home cages. 17beta-Estradiol or cholesterol prevented stress-induced CA3 dendritic retraction, increased CA1 apical spine density, and altered CA1 spine shape. The combination of chronic stress and 17beta-estradiol facilitated water maze acquisition compared to chronic stress + blank implants and nonstressed controls + 17beta-estradiol. To further investigate the interaction between 17beta-estradiol and stress on hippocampal morphology, experiment 2 was conducted on gonadally intact, cycling female rats that were chronically restrained (6h/d/21d), and then euthanized at proestrus (high ovarian hormones) or estrus (low ovarian hormones). Cycling female rats failed to show chronic stress-induced CA3 dendritic retraction at either estrous phase. Chronic stress enhanced the ratio of CA1 basal spine heads to headless spines as found in experiment 1. In addition, proestrous rats displayed increased CA1 spine density regardless of stress history. These results show that 17beta-estradiol or cholesterol protect against chronic stress-induced CA3 dendritic retraction in females. These stress- and 17beta-estradiol-induced morphological changes may provide insight into how dendritic complexity and spine properties contribute to spatial ability.
2007
Scharfman, Helen E; Hintz, Tana M; Gomez, Juan; Stormes, Kerry A; Barouk, Sharon; Malthankar-Phatak, Gauri H; McCloskey, Daniel P; Luine, Victoria N; Maclusky, Neil J
Changes in hippocampal function of ovariectomized rats after sequential low doses of estradiol to simulate the preovulatory estrogen surge. Journal Article
In: Eur J Neurosci, vol. 26, no. 9, pp. 2595–2612, 2007, ISSN: 0953-816X (Print); 0953-816X (Linking).
@article{Scharfman2007,
title = {Changes in hippocampal function of ovariectomized rats after sequential low doses of estradiol to simulate the preovulatory estrogen surge.},
author = {Helen E Scharfman and Tana M Hintz and Juan Gomez and Kerry A Stormes and Sharon Barouk and Gauri H Malthankar-Phatak and Daniel P McCloskey and Victoria N Luine and Neil J Maclusky},
url = {https://www.ncbi.nlm.nih.gov/pubmed/17970745},
doi = {10.1111/j.1460-9568.2007.05848.x},
issn = {0953-816X (Print); 0953-816X (Linking)},
year = {2007},
date = {2007-10-26},
journal = {Eur J Neurosci},
volume = {26},
number = {9},
pages = {2595--2612},
address = {Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, West Haverstraw, NY 10962, USA. hscharfman@nki.rfmh.org},
abstract = {In adult female rats, robust hippocampal changes occur when estradiol rises on the morning of proestrus. Whether estradiol mediates these changes, however, remains unknown. To address this issue, we used sequential injections of estradiol to simulate two key components of the preovulatory surge: the rapid rise in estradiol on proestrous morning, and the slower rise during the preceding day, diestrus 2. Animals were examined mid-morning of simulated proestrus, and compared to vehicle-treated or intact rats. In both simulated and intact rats, CA1-evoked responses were potentiated in hippocampal slices, and presynaptic mechanisms appeared to contribute. In CA3, multiple population spikes were evoked in response to mossy fiber stimuli, and expression of brain-derived neurotrophic factor was increased. Simulation of proestrous morning also improved performance on object and place recognition tests, in comparison to vehicle treatment. Surprisingly, effects on CA1-evoked responses showed a dependence on estradiol during simulated diestrus 2, as well as a dependence on proestrous morning. Increasing estradiol above the physiological range on proestrous morning paradoxically decreased evoked responses in CA1. However, CA3 pyramidal cell activity increased further, and became synchronized. Together, the results confirm that physiological estradiol levels are sufficient to profoundly affect hippocampal function. In addition: (i) changes on proestrous morning appear to depend on slow increases in estradiol during the preceding day; (ii) effects are extremely sensitive to the peak serum level on proestrous morning; and (iii) there are striking subfield differences within the hippocampus.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In adult female rats, robust hippocampal changes occur when estradiol rises on the morning of proestrus. Whether estradiol mediates these changes, however, remains unknown. To address this issue, we used sequential injections of estradiol to simulate two key components of the preovulatory surge: the rapid rise in estradiol on proestrous morning, and the slower rise during the preceding day, diestrus 2. Animals were examined mid-morning of simulated proestrus, and compared to vehicle-treated or intact rats. In both simulated and intact rats, CA1-evoked responses were potentiated in hippocampal slices, and presynaptic mechanisms appeared to contribute. In CA3, multiple population spikes were evoked in response to mossy fiber stimuli, and expression of brain-derived neurotrophic factor was increased. Simulation of proestrous morning also improved performance on object and place recognition tests, in comparison to vehicle treatment. Surprisingly, effects on CA1-evoked responses showed a dependence on estradiol during simulated diestrus 2, as well as a dependence on proestrous morning. Increasing estradiol above the physiological range on proestrous morning paradoxically decreased evoked responses in CA1. However, CA3 pyramidal cell activity increased further, and became synchronized. Together, the results confirm that physiological estradiol levels are sufficient to profoundly affect hippocampal function. In addition: (i) changes on proestrous morning appear to depend on slow increases in estradiol during the preceding day; (ii) effects are extremely sensitive to the peak serum level on proestrous morning; and (iii) there are striking subfield differences within the hippocampus.
McLaughlin, Katie J; Gomez, Juan L; Baran, Sarah E; Conrad, Cheryl D
The effects of chronic stress on hippocampal morphology and function: an evaluation of chronic restraint paradigms. Journal Article
In: Brain Res, vol. 1161, pp. 56–64, 2007, ISSN: 0006-8993 (Print); 0006-8993 (Linking).
@article{McLaughlin2007,
title = {The effects of chronic stress on hippocampal morphology and function: an evaluation of chronic restraint paradigms.},
author = {Katie J McLaughlin and Juan L Gomez and Sarah E Baran and Cheryl D Conrad},
url = {https://www.ncbi.nlm.nih.gov/pubmed/17603026},
doi = {10.1016/j.brainres.2007.05.042},
issn = {0006-8993 (Print); 0006-8993 (Linking)},
year = {2007},
date = {2007-06-02},
journal = {Brain Res},
volume = {1161},
pages = {56--64},
address = {Department of Psychology, Arizona State University, Tempe, AZ 85287-1104, USA. kjmclaugh@hotmail.com},
abstract = {Chronic restraint stress for 6 h/21 days causes hippocampal CA3 apical dendritic retraction, which parallels spatial memory impairments in male rats. Recent research suggests that chronic immobilization stress for 2 h/10 days induces CA3 dendritic retraction [Vyas, A., Mitra, R., Shankaranarayana Rao, B.S., Chattarji, S., 2002. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J. Neurosci. 22, 6810-6818.] and questions whether CA3 dendritic retraction and spatial memory deficits can be produced sooner than found following 6 h/21 days of restraint stress. Therefore, this study investigated the effects of four different durations of chronic restraint stress (varied by hours/day and total number of days) and the subsequent effects on hippocampal CA3 morphology and spatial memory in the same male Sprague-Dawley rats. The results showed that only rats exposed to the 6 h/21 days restraint paradigm exhibited CA3 apical dendritic retraction, consistent spatial memory deficits, and decreased body weight gain compared to experimental counterparts and controls. While chronically stressing a rat with wire mesh restraint has a physical component, it acts primarily as a psychological stressor, and these findings support the interpretation that chronic psychological stress produces hippocampal-dependent cognitive deficits that are consistent with hippocampal structural changes. Differences in stress effects observed across different studies may be due to rat strain, type of stressor, and housing conditions; however, the current findings support the use of chronic restraint stress, with wire mesh, for 6 h/21 days as a reliable and efficient method to produce psychological stress and to cause CA3 dendritic retraction and spatial memory deficits in male Sprague-Dawley rats.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Chronic restraint stress for 6 h/21 days causes hippocampal CA3 apical dendritic retraction, which parallels spatial memory impairments in male rats. Recent research suggests that chronic immobilization stress for 2 h/10 days induces CA3 dendritic retraction [Vyas, A., Mitra, R., Shankaranarayana Rao, B.S., Chattarji, S., 2002. Chronic stress induces contrasting patterns of dendritic remodeling in hippocampal and amygdaloid neurons. J. Neurosci. 22, 6810-6818.] and questions whether CA3 dendritic retraction and spatial memory deficits can be produced sooner than found following 6 h/21 days of restraint stress. Therefore, this study investigated the effects of four different durations of chronic restraint stress (varied by hours/day and total number of days) and the subsequent effects on hippocampal CA3 morphology and spatial memory in the same male Sprague-Dawley rats. The results showed that only rats exposed to the 6 h/21 days restraint paradigm exhibited CA3 apical dendritic retraction, consistent spatial memory deficits, and decreased body weight gain compared to experimental counterparts and controls. While chronically stressing a rat with wire mesh restraint has a physical component, it acts primarily as a psychological stressor, and these findings support the interpretation that chronic psychological stress produces hippocampal-dependent cognitive deficits that are consistent with hippocampal structural changes. Differences in stress effects observed across different studies may be due to rat strain, type of stressor, and housing conditions; however, the current findings support the use of chronic restraint stress, with wire mesh, for 6 h/21 days as a reliable and efficient method to produce psychological stress and to cause CA3 dendritic retraction and spatial memory deficits in male Sprague-Dawley rats.
