Effects of kappa opioids on schedule-controlled behavior of squirrel monkeys.
The behavioral effects of U50,488 [( trans]-3,4-dichloro-N-methyl-N[2-(1- pyrrolidinyl)cyclohexyl]benzeneacetamide), bremazocine, Mr2266 [(-)-5,9-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphan] and morphine were compared in squirrel monkeys responding under multiple fixed-ratio fixed-interval (FR FI) schedules of food presentation or stimulus-shock termination. Doses of bremazocine (0.001-0.003 mg/kg), U50,488 (0.03-0.1 mg/kg) and Mr2266 (1.0-3.0 mg/kg) that markedly increased overall rates of FI responding maintained by stimulus-shock termination had little effect on or only decreased overall rates of FI responding maintained by food presentation. Each of the kappa opioids decreased FR responding maintained by either consequence. Morphine (0.03-1.7 mg/kg) only decreased responding under all conditions. Pretreatment with Mr2266 (0.1 mg/kg) produced a 10-fold or more rightward shift in the dose-effect functions for morphine under the two multiple schedules and U50,488 under the multiple schedule of food presentation. A 3-fold higher dose of Mr2266 produced an approximately 10-fold rightward shift in the descending portion of the dose-effect functions for U50,488 and bremazocine under the schedule of stimulus-shock termination but did not appreciably alter their rate-increasing effects. Naltrexone (0.1 mg/kg) antagonized the effects of selected doses of morphine or bremazocine on overall rates of responding under the schedule of stimulus-shock termination. In contrast to its effects in combination with morphine, however, naltrexone (0.1-3.0 mg/kg) did not block alterations in patterns of FI responding produced by bremazocine.(ABSTRACT TRUNCATED AT 250 WORDS)
Bergman
J
J
Laboratory of Psychobiology, Harvard Medical School, Southborough, Massachusetts.
Warren
P H
PH
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D008297:Male; D009019:Morphinans / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects*; D017473:Receptors, Opioid, kappa; D012453:Saimiri
D000700:Analgesics; D001575:Benzomorphans; D009019:Morphinans; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; C027247:MR 2266; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C027248:bremazocine