Antagonism of the behavioral effects of 2,5-dimethoxy-4-methylamphetamine (DOM) and quipazine by metergoline.
The present study examined the disruptive effects of the phenethylamine hallucinogen 2,5-dimethoxy-4-methylamphetamine (DOM) and the putative 5-hydroxytryptamine (5-HT) agonist quipazine on fixed ratio-40 (FR-40) operant responding alone or after pretreatment with putative 5-HT antagonist metergoline. Food-deprived male rats were trained to bar press on a FR-40 schedule for food reinforcements; control responding under this schedule is characterized by a rapid, constant rate of responding (approximately 100 response/min). In control animals, both DOM and quipazine produced dose-dependent disruptions of FR-40 performance characterized by periods of non-responding or "pausing". Following pretreatment with 1.0 mg/kg, and to a lesser extent 0.1 mg/kg, metergoline (180 min prior to the session) the dose-response curves for the "pausing" produced by both DOM and quipazine were shifted significantly to the right. Moreover, increasing the dose of DOM about 16-fold and that of quipazine about 8-fold appears to completely override the antagonism by 1 mg/kg metergoline. These results suggest that the "pausing" produced by DOM or quipazine is the result of activation of 5-HT receptors.
D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine / Q000037:antagonists & inhibitors*; D000662:Amphetamines / Q000037:antagonists & inhibitors*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003216:Conditioning, Operant / Q000187:drug effects; D004873:Ergolines / Q000494:pharmacology*; D008297:Male; D008711:Metergoline / Q000494:pharmacology*; D011804:Quinolines / Q000037:antagonists & inhibitors*; D011814:Quipazine / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012055:Reinforcement Schedule
D000662:Amphetamines; D004873:Ergolines; D011804:Quinolines; D008711:Metergoline; D004290:DOM 2,5-Dimethoxy-4-Methylamphetamine; D011814:Quipazine