Kappa agonist and antagonist properties of mixed action opioids in a pigeon drug discrimination procedure.
Previous investigations indicate that mixed action opioids (i.e., opioids with activity at a combination of opioid receptor sites or a combination of opioid and nonopioid sites) often possess kappa-like stimulus effects in the rat and monkey, but mu-like stimulus effects in pigeons. In the present investigation, the kappa agonist and antagonist actions of a series of mixed action opioids were examined in pigeons trained to discriminate a 0.017-mg/kg dose of the kappa agonist bremazocine from saline. The mixed-action opioids (-)-n-allylnormetazocine, (-)-cyclazocine, (-)-metazocine, levallorphan, buprenorphine, nalbuphine, butorphanol and nalorphine failed to substitute for the bremazocine stimulus. When administered in combination with the training dose of bremazocine, each of these opioids produced a dose-related antagonism of the bremazocine stimulus. With the exceptions of butorphanol and (-)-metazocine, the antagonist effects of these opioids were surmountable. Buprenorphine, (-)-n-allylnormetazocine and levallorphan produced their kappa antagonist effects at doses approximately 2 to 3 log units lower than those that decreased rates of responding when these opioids were administered alone, whereas approximately 1 log unit separated the kappa antagonist and rate-decreasing effects of nalorphine, nalbuphine and (-)-cyclazocine. In contrast, the kappa antagonist effects of butorphanol and (-)-metazocine were observed only at doses of markedly decreased response rates. A somewhat different profile was obtained with ethylketocyclazocine and ketocyclazocine in that these mixed action opioids produced partial substitution for and partial antagonism of the bremazocine stimulus.(ABSTRACT TRUNCATED AT 250 WORDS)
Picker
M J
MJ
Department of Psychology, University of North Carolina at Chapel Hill.
D000818:Animals; D001575:Benzomorphans / Q000494:pharmacology; D010856:Columbidae; D004193:Discrimination Learning / Q000187:drug effects*; D005260:Female; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000187:drug effects*; D012965:Sodium Chloride / Q000494:pharmacology
D001575:Benzomorphans; D009292:Narcotic Antagonists; D009294:Narcotics; D017473:Receptors, Opioid, kappa; D012965:Sodium Chloride; C027248:bremazocine