Opiate-agonist induced taste aversion learning in the Fischer 344 and Lewis inbred rat strains: evidence for differential mu opioid receptor activation.
The Fischer 344 (F344) and Lewis (LEW) inbred rat strains react differently to morphine in a number of behavioral and physiological preparations, including the acquisition of aversions induced by this compound. The present experiment tested the ability of various compounds with relative selectivity at kappa, delta and mu receptor subtypes to assess the relative roles of these subtypes in mediating the differential aversive effects of morphine in the two strains. In the assessment of the role of the kappa receptor in morphine-induced aversions, animals in both strains were given access to saccharin followed by varying doses of the kappa agonist (-)-U50,488H (0.0, 0.28, 0.90 and 1.60 mg/kg). Although (-)-U50,488H induced aversions in both strains, no strain differences emerged. A separate subset of subjects was trained with the selective delta opioid agonist, SNC80 (0.0, 5.6, 10.0 and 18.0 mg/kg), and again although SNC80 induced aversions, there were no strain differences. Finally, a third subset of subjects was trained with heroin (0.0, 3.2, 5.6 and 10.0 mg/kg), a compound with activity at all three opiate receptor subtypes. Although heroin induced aversions in both strains, the aversions were significantly greater in the F344 strain, suggesting that differential activation of the mu opioid receptor likely mediates the reported strain differences in morphine-induced aversion learning. These data were discussed in terms of strain differences in opioid system functioning and the implications of such differences for other morphine-induced behavioral effects reported in F344 and LEW rats.
Davis
Catherine M
CM
Psychopharmacology Laboratory, American University, Washington, DC 20016, United States. cd2994a@american.edu
Rice
Kenner C
KC
Riley
Anthony L
AL
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001549:Benzamides / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D003932:Heroin / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000235:genetics; D017473:Receptors, Opioid, kappa / Q000819:agonists / Q000235:genetics; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000235:genetics; D013045:Species Specificity; D013649:Taste / Q000187:drug effects*
D001549:Benzamides; D009294:Narcotics; D010879:Piperazines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C088464:4-(alpha-(4-allyl-2,5-dimethyl-1-piperazinyl)-3-methoxybenzyl)-N,N-diethylbenzamide; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D003932:Heroin