Abstract
This study examined the effects of a nonselective opiate antagonist and antagonists selective for the μ1 versus δ opioid receptor on ethanol-seeking behavior induced by alcohol-related environmental stimuli in an animal model of relapse. Rats were trained to self-administer ethanol (10% w/v) or water on an FR 1 schedule in 30-min daily sessions. The availability of ethanol was signaled by an olfactory discriminative stimulus (S+). A different olfactory stimulus (S−) signaled water availability. In addition, each lever-response resulting in delivery of ethanol was paired with illumination of a visual cue for 5 s (SC+), whereas a 5-s white noise (SC−) was associated with water. The rats were then subjected to a 20-day extinction phase where lever presses had no programmed consequences. Reexposure to the S+/CS+ stimulus condition in the absence of further ethanol availability elicited strong recovery of responding. No effect was observed following presentation of S−/CS−. Subsequentely, ethanol-seeking behavior associated with the S+/CS+ stimulus condition was studied in rats treated with the nonselective opiate antagonist naltrexone (0.25–1 mg/kg, SC), the δ selective antagonist naltrindole (1–5 mg/kg, IP), and the μ1 selective antagonist naloxonazine (1–15 mg/kg, IP). Naltrexone (1 mg/kg) and naltrindole (5 mg/kg) selectively inhibited alcohol-seeking behavior. Naloxonazine (15 mg/kg) also reduced ethanol-seeking behavior but produced some nonselective behavioral suppression as well. The results provide evidence that selective blockade of either μ1 or δ opioid receptors inhibits ethanol-seeking behavior elicited by drug-related environmental stimuli. Moreover, the data suggest that drugs aimed at the δ opioid receptor may offer advantages in the treatment and prevention of relapse compared with agents that also block the μ1 receptor.
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This work is publication number 14027-NP from The Scripps Research Institute and was supported by NIAAA grant AA10531 (FW). The authors thank Miwe Arends for help with the preparation of the article.
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Please send reprint requests to: Friedbert Weiss, Ph.D., Department of Neuropharmacology (CVN-15), The Scripps Research Institute, La Jolla, CA 92037, USA. Fax: +1-858-784-7393, E-mail: bweiss@mail.scripps.edu
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Ciccocioppo, R., Martin-Fardon, R. & Weiss, F. Effect of Selective Blockade of μ1 or δ Opioid Receptors on Reinstatement of Alcohol-Seeking Behavior by Drug-Associated Stimuli in Rats . Neuropsychopharmacol 27, 391–399 (2002). https://doi.org/10.1016/S0893-133X(02)00302-0
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DOI: https://doi.org/10.1016/S0893-133X(02)00302-0
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