Risk for opioid abuse is diminished by inhibiting aldehyde dehydrogenase-2 (ALDH-2) in rats

Thumbnail Image



Journal Title

Journal ISSN

Volume Title

Repository Usage Stats


Citation Stats


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.






Published Version (Please cite this version)


Publication Info

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.

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.



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 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.


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 underlying cognitive function and addiction and to apply this knowledge to better understand cognitive dysfunction and addiction disorders and to develop novel therapeutic treatments.

The three main research components of his laboratory are focused on the themes of the basic neurobiology of cognition and addiction, neurobehavioral toxicology and the development of novel therapeutic treatments for cognitive dysfunction and substance abuse. Currently, our principal research focus concerns nicotine. We have documented the basic effects of nicotine on learning memory and attention as well as nicotine self-administration. We are continuing with more mechanistic studies in rat models using selective lesions, local infusions and neurotransmitter interaction studies. We have found that nicotine improves memory performance not only in normal rats, but also in rats with lesions of hippocampal and basal forebrain connections. We are concentrating on alpha7 and alpha4beta2 nicotinic receptor subtypes in the hippocampus, amygdala , thalamus and frontal cortex and how they interact with dopamine D1 and D2 and glutamate NMDA systems with regard to memory and addiction. I am also conducting studies on human cognitive behavior. We have current studies to assess nicotine effects on attention, memory and mental processing speed in schizophrenia, Alzheimer's Disease and Attention Deficit Hyperactivity Disorder. In the area of neurobehavioral toxicology, I have continuing projects to characterize the adverse effects of prenatal and adolescent nicotine exposure. Our primary project in neurobehavioral toxicology focuses on the cognitive deficits caused by the marine toxins. The basic and applied aims of our research complement each other nicely. The findings concerning neural mechanisms underlying cognitive function help direct the behavioral toxicology and therapeutic development studies, while the applied studies provide important functional information concerning the importance of the basic mechanisms under investigation.

Unless otherwise indicated, scholarly articles published by Duke faculty members are made available here with a CC-BY-NC (Creative Commons Attribution Non-Commercial) license, as enabled by the Duke Open Access Policy. If you wish to use the materials in ways not already permitted under CC-BY-NC, please consult the copyright owner. Other materials are made available here through the author’s grant of a non-exclusive license to make their work openly accessible.