Dextromethorphan and bupropion reduces high level remifentanil self-administration in rats.
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.
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https://hdl.handle.net/10161/20571Published Version (Please cite this version)
10.1016/j.pbb.2020.172919Publication 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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Show full item recordScholars@Duke
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
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
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
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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