Effects of receptor-selective opioids on operant behavior in morphine-treated and untreated rats.
Selective cross-tolerance is often used as evidence to differentiate opioid receptor subtypes. We used this strategy to study operant behavioral effects of the opioid peptides, [D-Ala2, NMePhe4, Gly-ol5]enkephalin (DAGO), [D-Pen2.5]-enkephalin (DPDPE) and dynorphin, agonists highly selective for mu, delta, and kappa receptors, respectively. Food-deprived rats were trained to lever-press on a fixed-interval 3-min schedule of food-reinforcement. Time-effect and dose-effect curves were generated for each of the peptides, as well as for morphine, administered ICV, 5 min prior to the 1-h operant session. Experiments were performed on untreated subjects and on subjects receiving chronic infusion of morphine (10 mg/kg/day) from osmotic pumps. In untreated animals, morphine and the mu-selective peptide, DAGO, induced relatively long-lasting dose-related decreases in responding, whereas the non-mu agonists, DPDPE and dynorphin, induced only transient effects: response rates increased at low doses and decreased at high doses. Animals receiving chronic morphine infusion were tolerant to the rate-decreasing effects of morphine and DAGO; ED50s increased by factors of 8 and 6, respectively. There was some evidence of cross-tolerance to DPDPE and of sensitization to dynorphin in the morphine-maintained animals.
Adams
J U
JU
Department of Pharmacology, Emory University School of Medicine, Atlanta, GA 30322.
Holtzman
S G
SG
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005502:Food; D007262:Infusions, Intravenous; D007276:Injections, Intraventricular; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*
D004745:Enkephalins; D009294:Narcotics; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004399:Dynorphins; D009020:Morphine; D020881:Enkephalin, D-Penicillamine (2,5)-