Repeated acquisition of behavioral chains in squirrel monkeys: comparisons of a mu, kappa and delta opioid agonist.
Responding by squirrel monkeys was maintained by food presentation under a repeated acquisition of behavioral chains procedure. Monkeys acquired a different three-response chain each session. Sequence completions were reinforced under a fixed-ratio 5 schedule, whereas errors produced a brief time out. Morphine (0.1-3.2 mg/kg) produced dose-related decreases in response rate at doses that had little or no effect on errors. U50488H ([trans]3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)- cyclohexyl]benzeneacetamide methane sulfonate hydrate) (0.018-0.56 mg/kg) yielded a steep dose-effect curve, decreasing response rate only at high doses that also had little or no effect on errors. The delta opioid agonist BW373U86 (+/-)-4-((alpha-R*)-alpha-((2S*,5R*)-4-allyl-2,5-dimethyl-1- piperazinyl)-3-hydroxybenzyl)-N,N-diethylbenzamide dihydrochloride (0.0056-0.32 mg/kg) produced dose-related decreases in response rate and increased errors. The delta opioid receptor antagonist naltrindole (0.056-18 mg/kg) alone had no effect on either the rate of responding or percent errors. The rate-decreasing and error-increasing effects produced by BW373U86 were antagonized by naltrindole. BW373U86 alone at doses of > or = 0.56 mg/kg produced brief tonic-clonic convulsions in all monkeys. Naltrindole (1 mg/kg) also antagonized the convulsant effects of BW373U86. At doses at which naltrindole was an effective antagonist of BW373U86, it failed to antagonize either morphine or U50488H. These results demonstrate that the delta opioid agonist BW373U86 produces effects on acquisition that differ dramatically from prototypical mu and kappa opioid agonists.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Medical Center, New Orleans 70112-1393.
E D
ED
Pakarinen
J H
JH
Woods
J M
JM
Moerschbaecher
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D017450:Receptors, Opioid, mu / Q000819:agonists*; D012453:Saimiri
D001549:Benzamides; D010879:Piperazines; D011759:Pyrrolidines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C083877:BW 373U86; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C055382:naltrindole