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Dextromethorphan and bupropion reduces high level remifentanil self-administration in rats.

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Date
2020-04
Authors
Blair, Graham
Wells, Corinne
Ko, Ashley
Modarres, John
Pace, Caroline
Davis, James M
Rezvani, Amir H
Rose, Jed E
Levin, Edward D
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Abstract
Opiate addiction has risen substantially during the past decade. New treatments to combat opiate addiction are sorely needed. The current study was conducted to determine the acute individual and interactive effects of bupropion and dextromethorphan in a rat model of opiate self-administration using the short-acting synthetic opioid remifentanil. Both of these drugs have been found to reduce self-administration of nicotine. Bupropion and dextromethorphan and their combination had differential effects depending on whether the rats showed higher or lower baseline remifentanil self-administration. The rats with higher initial remifentanil self-administration showed a significant decrease in remifentanil self-administration with bupropion or dextromethorphan treatment, compared to the vehicle control condition. This decrease in self-remifentanil administration was most pronounced when combination of the higher doses of bupropion and dextromethorphan were administered. In contrast, the rats with lower baseline remifentanil self-administration showed the opposite effect of drug treatment with an increase in remifentanil self-administration with bupropion treatment compared to the vehicle control condition. Dextromethorphan had no significant effect inthis group. This study shows that combination bupropion and dextromethorphan affects remifentanil self-administration in a complex fashion with differential effects on low and high baseline responders. In subjects with high baseline remifentanil self-administration, bupropion and dextromethorphan treatment significantly reduced self-administration, whereas in subjects with low baseline remifentanil self-administration, bupropion increased remifentanil self-administration and dextromethorphan had no discernible effect. This finding suggests that combination bupropion-dextromethorphan should be tested in humans, with a focus on treating people with high-level opiate use.
Type
Journal article
Subject
Bupropion
Dextromethorphan
Opioids
Rats
Remifentanil
Self-administration
Permalink
https://hdl.handle.net/10161/20571
Published Version (Please cite this version)
10.1016/j.pbb.2020.172919
Publication Info
Blair, Graham; Wells, Corinne; Ko, Ashley; Modarres, John; Pace, Caroline; Davis, James M; ... Levin, Edward D (2020). Dextromethorphan and bupropion reduces high level remifentanil self-administration in rats. Pharmacology, biochemistry, and behavior, 193. pp. 172919. 10.1016/j.pbb.2020.172919. Retrieved from https://hdl.handle.net/10161/20571.
This is constructed from limited available data and may be imprecise. To cite this article, please review & use the official citation provided by the journal.
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Scholars@Duke

Davis

James Davis

Associate Professor of Medicine
Dr. James Davis is a practicing physician of Internal Medicine, and serves as the Medical Director for Duke Center for Smoking Cessation, Director of the Duke Smoking Cessation Program and Co-Director of the Duke-UNC Tobacco Treatment Specialist Credentialing Program.  His research focuses on development of new pharmaceutical treatments for smoking cessation.  He is principal investigator on several trials including a study on “adaptive” smoking cessation and several trials
Levin

Edward Daniel Levin

Professor in Psychiatry and Behavioral Sciences
Dr. Levin is Chief of the Neurobehavioral Research Lab in the Psychiatry Department of Duke University Medical Center. His primary academic appointment is as Professor in the Department of Psychiatry and Behavioral Sciences. He also has secondary appointments in the Department Pharmacology and Cancer Biology, the Department of Psychological and Brain Sciences and the Nicholas School of the Environment at Duke. His primary research effort is to understand basic neural interactions underlyi
Rezvani

Amir H. Rezvani

Professor Emeritus in Psychiatry and Behavioral Sciences
My research and teaching interests have been primarily focused on the following areas: Alcoholism: I work with "alcoholic" rats with genetic predisposition!" We use selectively-bred alcohol preferring rats as an animal model of human alcoholism for developing better pharmacological treatments for alcoholism. Recently, we are working on several novel promissing "anti-craving" compounds for the treatment of alcoholism. We are also studing the interaction be
Rose

Jed Eugene Rose

Professor Emeritus in Psychiatry and Behavioral Sciences
We are pursuing three main lines of research: 1) Brain imaging of the effects of nicotine and cigarette smoking: We have used Positron Emission Tomography (PET) methods to analyze regional cerebral blood flow responses to nicotine, administered either intravenously or inhaled in cigarettes. Our aim is to identify brain substrates mediating the addictive properties of nicotine. Preliminary results have shown alterations in the pattern of regional cerebral blood flow, involving
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