Comparison of the effects of naloxone and picrotoxin on schedule-controlled responding in the pigeon: possible GABA-antagonistic effects of naloxone.
The effects of naloxone and picrotoxin were determined alone and in conjunction with pentobarbital, diazepam or clonazepam, in pigeons responding under a multiple fixed-ratio 30-response, fixed-interval 5-min schedule of food presentation. Naloxone (10.0-80.0 mg/kg i.m.) and picrotoxin (0.1-0.56 mg/kg i.m.) alone produced only dose-related decreases in responding in both fixed-ratio and fixed-interval components. Pentobarbital (3.0 and 10.0 mg/kg i.m.) administered in combination with naloxone and picrotoxin shifted dose-response curves for both naloxone and picrotoxin to the right. In contrast, both diazepam (1.0-10.0 mg/kg p.o.) and clonazepam (0.3-3.0 mg/kg p.o.) attenuated the rate-decreasing effects of 0.56 mg/kg of picrotoxin, but not those of 80.0 mg/kg of naloxone. Dose-effect curves for naloxone and picrotoxin were then determined during daily administration of 10.0 mg/kg of diazepam. Dose-response curves for both naloxone and picrotoxin were shifted to the right under these conditions. These data support previous evidence that naloxone exerts gamma-aminobutyric acid-antagonistic effects in addition to its potent opioid-antagonistic effects.
D000818:Animals; D002998:Clonazepam / Q000494:pharmacology; D010856:Columbidae; D003216:Conditioning, Operant / Q000187:drug effects*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004361:Drug Tolerance; D018756:GABA Antagonists; D008297:Male; D009270:Naloxone / Q000494:pharmacology*; D010424:Pentobarbital / Q000494:pharmacology; D010852:Picrotoxin / Q000494:pharmacology*
D002998:Clonazepam; D003975:Diazepam; D018756:GABA Antagonists; D009270:Naloxone; D010424:Pentobarbital; D010852:Picrotoxin