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Renata C. N. Marchette, Pharm.D., Ph.D.

Renata C. N. Marchette, Pharm.D., Ph.D.

Position

Research Fellow , Neurobiology of Addiction Section

Contact

Biomedical Research Center
251 Bayview Blvd.
Suite 200
Room 08A505.18
Baltimore, MD 21224

Phone: 443-740-2730

Email: renata.marchette@nih.gov

Education

Ph.D. in Pharmacology - Universidade Federal de Santa Catarina, Florianopolis, SC, Brazil

M.Sc. in Pharmacology - Universidade Federal de Santa Catarina, Florianopolis, SC, Brazil

Pharm.D. - Universidade Estadual Paulista (UNESP), Araraquara, SP, Brazil

Research Interests

My long-term research interests are focused on the understanding of the neurobiological basis of psychiatric disorders and the pursuit of new treatments for these disorders. During my Ph.D. I systematically investigated the involvement of the HPA axis and the tachykinergic system in vulnerability and resilience to social defeat stress in mice. I joined the Koob Lab in 2018 and my research focuses on the involvement of brain stress systems and their sexual dimorphism in drug addiction. My goal is to identify new pharmacological targets for the understanding of drug addiction. I have systematically studied opioid seeking and taking behavior in a recently developed mouse model of opioid vapor self-administration in mice. Using modern techniques, I hope to uncover new druggable targets that are functionally linked to pathology and that can be modulated to facilitate recovery or confer resilience in mental disorders with a focus on addiction.

Selected Publications

Publications from the Neurobiology of Addiction Section.

2021

Marchette, Renata C N; Tunstall, Brendan J; Vendruscolo, Leandro F; Moussawi, Khaled

Operant Vapor Self-administration in Mice Journal Article

In: Bio Protoc, vol. 11, no. 10, pp. e4023, 2021, ISSN: 2331-8325.

Abstract | Links | BibTeX

@article{pmid34150930,
title = {Operant Vapor Self-administration in Mice},
author = {Renata C N Marchette and Brendan J Tunstall and Leandro F Vendruscolo and Khaled Moussawi},
url = {https://pubmed.ncbi.nlm.nih.gov/34150930/},
doi = {10.21769/BioProtoc.4023},
issn = {2331-8325},
year = {2021},
date = {2021-05-01},
urldate = {2021-05-01},
journal = {Bio Protoc},
volume = {11},
number = {10},
pages = {e4023},
abstract = {Models of drug addiction in rodents are instrumental in understanding the underlying neurobiology. Intravenous self-administration of drugs in mice is currently the most commonly used model; however, several challenges exist due to complications related to catheter patency. To take full advantage of the genetic tools available to study opioid addiction in mice, we developed a non-invasive mouse model of opioid self-administration using vaporized fentanyl. This model can be used to study various aspects of opioid addiction including self-administration, escalation of drug intake, extinction, reinstatement, and drug seeking despite adversity. Further, this model bypasses the limitations of intravenous self-administration and allows the investigation of drug taking over extended periods of time and in conjunction with cutting-edge techniques such as calcium imaging and electrophysiology.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Models of drug addiction in rodents are instrumental in understanding the underlying neurobiology. Intravenous self-administration of drugs in mice is currently the most commonly used model; however, several challenges exist due to complications related to catheter patency. To take full advantage of the genetic tools available to study opioid addiction in mice, we developed a non-invasive mouse model of opioid self-administration using vaporized fentanyl. This model can be used to study various aspects of opioid addiction including self-administration, escalation of drug intake, extinction, reinstatement, and drug seeking despite adversity. Further, this model bypasses the limitations of intravenous self-administration and allows the investigation of drug taking over extended periods of time and in conjunction with cutting-edge techniques such as calcium imaging and electrophysiology.

Close

  • https://pubmed.ncbi.nlm.nih.gov/34150930/
  • doi:10.21769/BioProtoc.4023

Close

Marchette, Renata C N; Gregory-Flores, Adriana; Tunstall, Brendan J; Carlson, Erika R; Jackson, Shelley N; Sulima, Agnieszka; Rice, Kenner C; Koob, George F; Vendruscolo, Leandro F

κ-Opioid receptor antagonism reverses heroin withdrawal-induced hyperalgesia in male and female rats Journal Article

In: Neurobiol Stress, vol. 14, pp. 100325, 2021, ISSN: 2352-2895.

Abstract | Links | BibTeX

@article{pmid33997152,
title = {κ-Opioid receptor antagonism reverses heroin withdrawal-induced hyperalgesia in male and female rats},
author = {Renata C N Marchette and Adriana Gregory-Flores and Brendan J Tunstall and Erika R Carlson and Shelley N Jackson and Agnieszka Sulima and Kenner C Rice and George F Koob and Leandro F Vendruscolo},
url = {https://pubmed.ncbi.nlm.nih.gov/33997152/},
doi = {10.1016/j.ynstr.2021.100325},
issn = {2352-2895},
year = {2021},
date = {2021-05-01},
urldate = {2021-05-01},
journal = {Neurobiol Stress},
volume = {14},
pages = {100325},
abstract = {Although opioids are potent analgesics, a consequence of chronic opioid use is hyperalgesia during withdrawal, which may contribute to opioid misuse. Dynorphin, the endogenous ligand of κ-opioid receptors (KORs), is upregulated in opioid-dependent rats and in animal models of chronic pain. However, the role of KORs in opioid withdrawal-induced hyperalgesia remains to be determined. We hypothesized that KOR antagonism would reverse opioid withdrawal-induced hyperalgesia in opioid-dependent rats. Male and female Wistar rats received daily injections of heroin (2-6 mg/kg, SC) and were tested for mechanical sensitivity in the electronic von Frey test 4-6 h into withdrawal. Female rats required significantly more heroin than male rats to reach comparable levels of both heroin-induced analgesia and hyperalgesia (6 mg/kg 2 mg/kg). Once hyperalgesia was established, we tested the effects of the KOR antagonists nor-binaltorphimine (norBNI; 30 mg/kg, SC) and 5'-guanidinonaltrindole (5'GNTI; 30 mg/kg, SC). When the animals continued to receive their daily heroin treatment (or saline treatment in the repeated saline group) five times per week throughout the experiment, both KOR antagonists reversed heroin withdrawal-induced hyperalgesia. The anti-hyperalgesia effect of norBNI was more prolonged in males than in females (14 days 7 days), whereas 5'GNTI had more prolonged effects in females than in males (14 days 4 days). The behavioral effects of 5'GNTI coincided with higher 5'GNTI levels in the brain than in plasma when measured at 24 h, whereas 5'GNTI did not reverse hyperalgesia at 30 min posttreatment when 5'GNTI levels were higher in plasma than in the brain. Finally, we tested the effects of 5'GNTI on naloxone-induced and spontaneous signs of opioid withdrawal and found no effect in either male or female rats. These findings indicate a functional role for KORs in heroin withdrawal-induced hyperalgesia that is observed in rats of both sexes.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Although opioids are potent analgesics, a consequence of chronic opioid use is hyperalgesia during withdrawal, which may contribute to opioid misuse. Dynorphin, the endogenous ligand of κ-opioid receptors (KORs), is upregulated in opioid-dependent rats and in animal models of chronic pain. However, the role of KORs in opioid withdrawal-induced hyperalgesia remains to be determined. We hypothesized that KOR antagonism would reverse opioid withdrawal-induced hyperalgesia in opioid-dependent rats. Male and female Wistar rats received daily injections of heroin (2-6 mg/kg, SC) and were tested for mechanical sensitivity in the electronic von Frey test 4-6 h into withdrawal. Female rats required significantly more heroin than male rats to reach comparable levels of both heroin-induced analgesia and hyperalgesia (6 mg/kg 2 mg/kg). Once hyperalgesia was established, we tested the effects of the KOR antagonists nor-binaltorphimine (norBNI; 30 mg/kg, SC) and 5'-guanidinonaltrindole (5'GNTI; 30 mg/kg, SC). When the animals continued to receive their daily heroin treatment (or saline treatment in the repeated saline group) five times per week throughout the experiment, both KOR antagonists reversed heroin withdrawal-induced hyperalgesia. The anti-hyperalgesia effect of norBNI was more prolonged in males than in females (14 days 7 days), whereas 5'GNTI had more prolonged effects in females than in males (14 days 4 days). The behavioral effects of 5'GNTI coincided with higher 5'GNTI levels in the brain than in plasma when measured at 24 h, whereas 5'GNTI did not reverse hyperalgesia at 30 min posttreatment when 5'GNTI levels were higher in plasma than in the brain. Finally, we tested the effects of 5'GNTI on naloxone-induced and spontaneous signs of opioid withdrawal and found no effect in either male or female rats. These findings indicate a functional role for KORs in heroin withdrawal-induced hyperalgesia that is observed in rats of both sexes.

Close

  • https://pubmed.ncbi.nlm.nih.gov/33997152/
  • doi:10.1016/j.ynstr.2021.100325

Close

2020

Moussawi, K; Ortiz, M M; Gantz, S C; Tunstall, B J; Marchette, R C N; Bonci, A; Koob, G F; Vendruscolo, L F

Fentanyl vapor self-administration model in mice to study opioid addiction. Journal Article

In: Sci Adv, vol. 6, no. 32, pp. eabc0413, 2020.

Abstract | Links | BibTeX

@article{Moussawi:2020aa,
title = {Fentanyl vapor self-administration model in mice to study opioid addiction.},
author = {K Moussawi and M M Ortiz and S C Gantz and B J Tunstall and R C N Marchette and A Bonci and G F Koob and L F Vendruscolo},
url = {https://pubmed.ncbi.nlm.nih.gov/32821843/},
doi = {10.1126/sciadv.abc0413},
year = {2020},
date = {2020-08-01},
urldate = {2020-08-01},
journal = {Sci Adv},
volume = {6},
number = {32},
pages = {eabc0413},
abstract = {Intravenous drug self-administration is considered the "gold standard" model to investigate the neurobiology of drug addiction in rodents. However, its use in mice is limited by frequent complications of intravenous catheterization. Given the many advantages of using mice in biomedical research, we developed a noninvasive mouse model of opioid self-administration using vaporized fentanyl. Mice readily self-administered fentanyl vapor, titrated their drug intake, and exhibited addiction-like behaviors, including escalation of drug intake, somatic signs of withdrawal, drug intake despite punishment, and reinstatement of drug seeking. Electrophysiological recordings from ventral tegmental area dopamine neurons showed a lower amplitude of GABA(B) receptor-dependent currents during protracted abstinence from fentanyl vapor self-administration. This mouse model of fentanyl self-administration recapitulates key features of opioid addiction, overcomes limitations of the intravenous model, and allows investigation of the neurobiology of opioid addiction in unprecedented ways.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}

Close

Intravenous drug self-administration is considered the "gold standard" model to investigate the neurobiology of drug addiction in rodents. However, its use in mice is limited by frequent complications of intravenous catheterization. Given the many advantages of using mice in biomedical research, we developed a noninvasive mouse model of opioid self-administration using vaporized fentanyl. Mice readily self-administered fentanyl vapor, titrated their drug intake, and exhibited addiction-like behaviors, including escalation of drug intake, somatic signs of withdrawal, drug intake despite punishment, and reinstatement of drug seeking. Electrophysiological recordings from ventral tegmental area dopamine neurons showed a lower amplitude of GABA(B) receptor-dependent currents during protracted abstinence from fentanyl vapor self-administration. This mouse model of fentanyl self-administration recapitulates key features of opioid addiction, overcomes limitations of the intravenous model, and allows investigation of the neurobiology of opioid addiction in unprecedented ways.

Close

  • https://pubmed.ncbi.nlm.nih.gov/32821843/
  • doi:10.1126/sciadv.abc0413

Close

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  • HHS Vulnerability Disclosure
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