Antagonism of the discriminative effects of ethylketazocine, cyclazocine, and nalorphine in macaques.
dl-Ethylketazocine (EKC, 0.01 mg/kg) and saline were established as discriminative stimuli for food-maintained responding in macaque monkeys. Thirty consecutive presses on a right or left lever were reinforced with food, contingent on whether EKC or saline were administered before the session. For tests of antagonism, naltrexone, or UM 979 [(l)-5,9-alpha-dimethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphan] was administered concomitantly with EKC, dl-cyclazocine, or nalorphine. Both antagonists blocked completely the EKC discriminative stimulus. The antagonism of the stimulus and rate-altering effects of EKC was surmountable, with considerable intersubject variability in the magnitude of the EKC dose increase required to overcome the blockade. Cyclazocine and nalorphine, mixed agonist-antagonist opioids that share stimulus properties with EKC, were also susceptible to antagonism. Naltrexone antagonized completely the EKC stimulus effects of nalorphine; naltrexone and UM 979 antagonized completely the EKC stimulus effects of cyclazocine. Naltrexone antagonism of the cyclazocine stimulus was not surmountable, due to a lack of antagonism of the rate-decreasing effects of high cyclazocine doses.
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors*; D004192:Discrimination, Psychological; D016314:Ethylketocyclazocine; D008253:Macaca mulatta; D008254:Macaca nemestrina; D008297:Male; D009269:Nalorphine / Q000037:antagonists & inhibitors*; D009271:Naltrexone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*
D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D016314:Ethylketocyclazocine; D009271:Naltrexone; D003496:Cyclazocine; D009269:Nalorphine