Hippocampal mu-receptors mediate opioid reinforcement in the CA3 region.
Dependence on reinforcing chemicals is manifested when drug-seeking and drug-taking behaviors come to dominate the response repertoire. Clinical observations suggest that the craving and compulsive drug-seeking that characterize drug dependence are aroused by memories of the reinforcing drug experience. If so, a brain structure intimately associated with memory--the hippocampus--would be a plausible substrate for drug reinforcement effects. We report here that drug-naive rats rapidly learn to self-administer the opioid peptide dynorphin A in the CA3 region of hippocampus, and that this behavior is blocked by co-administration of the non-selective opiate antagonist naloxone. Subsequent studies demonstrated that coadministration of mu-, but not kappa- or delta-opioid antagonists also blocked self-administration behavior. We conclude that mu-receptors in the CA3 region of hippocampus may be important target sites for opioid dependence.
Department of Pharmacology, College of Medicine, University of California, Irvine 92717.
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Stevens
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Shiotsu
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Stein
D000818:Animals; D004399:Dynorphins / Q000008:administration & dosage / Q000494:pharmacology*; D004743:Enkephalin, Leucine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008297:Male; D009270:Naloxone / Q000008:administration & dosage / Q000494:pharmacology*; D009271:Naltrexone / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011712:Pyramidal Tracts / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D017450:Receptors, Opioid, mu; D012016:Reference Values; D012054:Reinforcement, Psychology; D012646:Self Administration
D009292:Narcotic Antagonists; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; C051844:norbinaltorphimine; D004743:Enkephalin, Leucine; D009271:Naltrexone; C024524:beta-funaltrexamine; D004399:Dynorphins; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine