Raul Garcia, Ph.D.

@article{Brackney:2021aa,

title = {Longer operant lever-press duration requirements induce fewer but longer response bouts in rats},

author = {Ryan J Brackney and Raul Garcia and Federico Sanabria},

url = {https://pubmed.ncbi.nlm.nih.gov/33629243/},

doi = {10.3758/s13420-021-00464-7},

isbn = {1543-4508},

year  = {2021},

date = {2021-01-01},

journal = {Learning & Behavior},

abstract = {Operant behavior is organized in bouts that are particularly visible under variable-interval (VI) schedules of reinforcement. Previous research showed that increasing the work required to produce a response decreases the rate at which bouts are emitted and increases the minimum interresponse time (IRT). In the current study, the minimum effective IRT was directly manipulated by changing the minimum duration of effective lever presses reinforced on a VI 40-s schedule. Contrary to assumptions of previous models, response durations were variable. Response durations were typically 0.5 s greater than the minimum duration threshold; durations that exceeded this threshold were approximately log-normally distributed. As the required duration threshold increased, rats emitted fewer but longer bouts. This effect may reflect an effort-induced reduction in motivation and a duration-induced facilitation of a response--outcome association.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Garcia:2020aa,

title = {Preclinical support for the therapeutic potential of zolmitriptan as a treatment for cocaine use disorders},

author = {Raul Garcia and Tien Le and Samantha N Scott and Delaram Charmchi and Jamie M L Sprout and Nathan S Pentkowski and Janet L Neisewander},

url = {https://pubmed.ncbi.nlm.nih.gov/32747623/},

doi = {10.1038/s41398-020-00956-6},

isbn = {2158-3188},

year  = {2020},

date = {2020-01-01},

journal = {Translational Psychiatry},

volume = {10},

number = {1},

pages = {266},

abstract = {Serotonin 1B receptor (5-HT1BR) agonists enhance cocaine intake in rats during daily self-administration but attenuate cocaine intake after prolonged abstinence. Here we investigated whether the less selective but clinically available 5-HT1D/1BR agonist, zolmitriptan, produces similar effects. Male and free-cycling female Sprague-Dawley rats were trained to lever press for cocaine (0.75 mg/kg, i.v.) or sucrose (45 mg pellet) reinforcement until performance rates stabilized. Rats then received zolmitriptan (3.0, 5.6, and 10 mg/kg, s.c.) prior to testing for its effects on response and reinforcement rates. Under cocaine testing conditions, rats had access to the training dose for the first hour followed by a lower cocaine dose (0.075 mg/kg, i.v.) for the second hour. Zolmitriptan decreased cocaine intake at both cocaine doses and in both sexes even without a period of abstinence and without altering sucrose intake. A separate group of rats underwent identical training procedures and were tested for effects of the selective 5-HT1B and 5-HT1D receptor antagonists, SB224289 (3.2, 5.6, and 10 mg/kg, s.c.) and BRL15572 (0.3, 1.0, and 3.0 mg/kg, i.p.), respectively, alone or in combination with zolmitriptan (5.6 mg/kg, s.c.) under identical cocaine testing procedures as above. The zolmitriptan-induced decrease in cocaine intake was reversed by SB224289 and to a lesser extent by BRL15572, suggesting that the effects of zolmitriptan involve both 5-HT1B and 5-HT1D receptors. Neither zolmitriptan, SB224289, or BRL15572 altered locomotor activity at the doses effective for modulating cocaine intake. These findings suggest that zolmitriptan has potential for repurposing as a treatment for cocaine use disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{10.1093/ijnp/pyx025,

title = {Preclinical Evidence That 5-HT1B Receptor Agonists Show Promise as Medications for Psychostimulant Use Disorders},

author = {Raul Garcia and Austin R Cotter and Kenneth Leslie and Foster M Olive and Janet L Neisewander},

url = {https://pubmed.ncbi.nlm.nih.gov/28444326/},

doi = {10.1093/ijnp/pyx025},

issn = {1461-1457},

year  = {2017},

date = {2017-01-01},

journal = {International Journal of Neuropsychopharmacology},

volume = {20},

number = {8},

pages = {644-653},

abstract = {5-HT1B receptor agonists enhance cocaine intake during daily self-administration sessions but decrease cocaine intake when tested after prolonged abstinence. We examined if 5-HT1B receptor agonists produce similar abstinence-dependent effects on methamphetamine intake.Male rats were trained to self-administer methamphetamine (0.1 mg/kg, i.v.) on low (fixed ratio 5 and variable ratio 5) and high (progressive ratio) effort schedules of reinforcement until intake was stable. Rats were then tested for the effects of the selective 5-HT1B receptor agonist, CP 94,253 (5.6 or 10 mg/kg), or the less selective but clinically available 5-HT1B/1D receptor agonist, zolmitriptan (10 mg/kg), on methamphetamine self-administration both before and after a 21-day forced abstinence period during which the rats remained in their home cages.The inverted U-shaped, methamphetamine dose-response function for intake on the fixed ratio 5 schedule was shifted downward by CP 94,253 both before and after abstinence. The CP 94,253-induced decrease in methamphetamine intake was replicated in rats tested on a variable ratio 5 schedule, and the 5-HT1B receptor antagonist SB 224,289 (10 mg/kg) reversed this effect. CP 94,253 also attenuated methamphetamine intake on a progressive ratio schedule both pre- and postabstinence. Similarly, zolmitriptan attenuated methamphetamine intake on a variable ratio 5 schedule both pre- and postabstinence, and the latter effect was sustained after each of 2 more treatments given every 2 to 3 days prior to daily sessions.Unlike the abstinence-dependent effect of 5-HT1B receptor agonists on cocaine intake reported previously, both CP 94,253 and zolmitriptan decreased methamphetamine intake regardless of abstinence. These findings suggest that 5-HT1B receptor agonists may have clinical efficacy for psychostimulant use disorders.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DANIELS2015238,

title = {Revisiting the effect of nicotine on interval timing},

author = {Carter W Daniels and Elizabeth Watterson and Raul Garcia and Gabriel J Mazur and Ryan J Brackney and Federico Sanabria},

url = {https://pubmed.ncbi.nlm.nih.gov/25637907/},

doi = {https://doi.org/10.1016/j.bbr.2015.01.027},

issn = {0166-4328},

year  = {2015},

date = {2015-01-01},

journal = {Behavioural Brain Research},

volume = {283},

pages = {238-250},

abstract = {This paper reviews the evidence for nicotine-induced acceleration of the internal clock when timing in the seconds-to-minutes timescale, and proposes an alternative explanation to this evidence: that nicotine reduces the threshold for responses that result in more reinforcement. These two hypotheses were tested in male Wistar rats using a novel timing task. In this task, rats were trained to seek food at one location after 8s since trial onset and at a different location after 16s. Some rats received the same reward at both times (group SAME); some received a larger reward at 16s (group DIFF). Steady baseline performance was followed by 3 days of subcutaneous nicotine administration (0.3mg/kg), baseline recovery, and an antagonist challenge (mecamylamine, 1.0mg/kg). Nicotine induced a larger, immediate reduction in latencies to switch (LTS) in group DIFF than in group SAME. This effect was sustained throughout nicotine administration. Mecamylamine pretreatment and nicotine discontinuation rapidly recovered baseline performance. These results support a response-threshold account of nicotinic disruption of timing performance, possibly mediated by nicotinic acetylcholine receptors. A detailed analysis of the distribution of LTSs suggests that anomalous effects of nicotine on LTS dispersion may be due to loss of temporal control of behavior.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}