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

@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}

}

@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}

}

@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}

}