Effects of opioid antagonists on unconditioned and conditioned hyperactivity to morphine.
In a series of experiments, the ability of selective mu- (beta-funaltrexamine, beta-FNA), delta- (naltrindole, nalt) and kappa- (nor-binaltorphimine, nor-BNI) opioid receptor antagonists to attenuate the unconditioned and conditioned hyperactive effects of morphine was examined. For comparison, the nonselective opioid receptor antagonist naloxone (nalx) was also examined. Locomotor activity served as the behavioral measure. Experiment 1 found that doses of 1 and 4, but not 16 mg/kg, of morphine effectively produced conditioned hyperactivity (CH). Experiments 2a-d found that beta-FNA, nalt, nor-BNI and nalx, respectively, attenuated unconditioned morphine-induced hyperactivity. Experiments 3a-c, however, found that none of the selective antagonists, given individually, attenuated CH. In contrast, nalx did attenuate CH (Experiment 3d). Collectively results suggest that the unconditioned and conditioned hyperactive responses to morphine are mediated by different receptor systems and that activation of multiple opioid-receptor subtypes mediate expression of CH.
Rauhut
Anthony S
AS
Department of Psychology, University of Kentucky, Lexington 40506-0044, USA. asrauh1@uky.edu
Gehrke
Brenda J
BJ
Phillips
Scott B
SB
Bardo
Michael T
MT
D000701:Analgesics, Opioid / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006948:Hyperkinesis / Q000139:chemically induced* / Q000523:psychology; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; C024524:beta-funaltrexamine; D009020:Morphine