Risk for opioid abuse is diminished by inhibiting aldehyde dehydrogenase-2 (ALDH-2) in rats
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2019-01-01
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Significant opiate addiction is known to follow prescribed opiate use for pain. There is a serious unmet need for non-addicting medications to prevent subsequent opiate addiction after a short period of opioid treatment for temporary pain. Recent evidence indicates that selective inhibition of aldehyde dehydrogenase-2 (ALDH-2) reduces drug-seeking and trained self-administration of alcohol, cocaine and nicotine, apparently by preventing a concomitant surge of dopamine in the ventral tegmental area (VTA) and nucleus accumbens (NAc). Activation of the same dopaminergic pathway is also implicated in opioid-induced reinforcement. Therefore, we asked whether the selective ALDH-2 inhibitor, ANS-6637, would attenuate opioid self-administration in drug-naïve rats for opioid self-administration. Rats received oral doses of ANS-6637 (9, 18, 36 or 72 mg/kg) or an equal volume of control vehicle 2 h before exposure to remifentanil and a light cue to accentuate self-administration over 5 consecutive days. Self-administration and the numbers of lever presses on both active and inactive levers were recorded. ANS-6637 significantly reduces remifentanil self-administration over 5 sessions of treatment in rats without prior exposure to remifentanil. We also confirm that the highest dose of ANS-6637 (72 mg/kg) used in this study did not prevent remifentanil-induced analgesia using a classic hot plate test. Thus, ANS-6637 significantly reduces of initial exposure to remifentanil self-administration without affecting desired analgesia. These preliminary observations suggest that ANS-6637 appears to have potential value as a non-addictive therapeutic agent to prevent abuse of commonly used opiates in initiating pain management.
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Rezvani, AH, C Wells, P Strumph, I Diamond, BK Blackburn and ED Levin (2019). Risk for opioid abuse is diminished by inhibiting aldehyde dehydrogenase-2 (ALDH-2) in rats. Journal of Drug and Alcohol Research, 8. 10.4303/jdar/236076 Retrieved from https://hdl.handle.net/10161/29518.
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Scholars@Duke
Amir H. Rezvani
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 promising "anti-craving" compounds for the treatment of alcoholism. We are also studying the interaction between alcohol drinking and nicotine intake.
Nicotine Addiction: We have been studying age and sex differences in i.v. nicotine self-administration in rats. We have found that pattern of drug intake is both age- and sex-dependent. Our lab is also exploring different neuronal targets for developing better pharmacologic treatment for nicotine addiction.
Sustained Attention: Another aspect of our research is studying the role of the neuronal nicotinic and other neuronal systems in sustained attention using a rodent model. We have shown, nicotine (not smoking!) and nicotinic compounds improve attention in rats. A majority of people with schizophrenia smoke and they smoke heavily. Thus, it is important to understand the interaction of antipsychotic medications and nicotine in sustained attention. This has been another aspect of our research with interesting results. Presently, we are testing novel nicotinic compounds for improving pharmacologically-impaired sustained attention.
Teaching: I love to teach and interact with students. Since arriving at Duke in 1999, I have been team-teaching the popular alcohol course (Psych 206-01R; Alcohol: Brain, Society and Individual). I also enjoy mentoring undergrad students who are interested in science and enjoy working in the lab with cute little creatures!.
Community: I am a member of the Board of Directors of Triangle Residential Options for Substance Abusers (TROSA), a self-supported therapeutic community in Durham. I also give seminars and workshops on addiction around the country.
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