Antagonism of the behavioral effects of 2,5-dimethoxy-4-methylamphetamine (DOM) and quipazine by metergoline.
Randall L. Commissaris, Richard H. Rech
Pharmacology, Biochemistry, and Behavior October 1981 DOI: 10.1016/0091-3057(81)90227-6 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experiment Peer reviewed |
|---|---|
| Population | Food-deprived male rats |
| Interventions | quipazine metergoline |
| Dose | metergoline 1.0 mg/kg and 0.1 mg/kg; DOM increased about 16-fold; quipazine increased about 8-fold |
| Key findings | DOM and quipazine each produced dose-dependent pausing in rats responding on a fixed-ratio-40 food-reinforcement schedule. Metergoline pretreatment at 1.0 mg/kg, and to a lesser extent 0.1 mg/kg, shifted both dose-response curves significantly to the right, and roughly 16-fold higher DOM or 8-fold higher quipazine appeared to override the 1 mg/kg metergoline antagonism. The authors suggest the pausing reflects activation of serotonin receptors. |
Abstract
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.
Citations in the library
Cited by 3
- The 5HT2 antagonist pirenperone reverses disruption of FR-40 by hallucinogenic drugs. Pharmacology, Biochemistry, and Behavior May 1985
- Naloxone alters the effects of LSD, DOM and quipazine on operant behavior of rats. Pharmacology, Biochemistry, and Behavior September 1984
- Neurotransmitter basis of the behavioral effects of hallucinogens. Neuroscience & Biobehavioral Reviews 1982
Cites 5
- Evidence for a central 5‐hydroxytryptamine receptor stimulation by lysergic acid diethylamide British Journal of Pharmacology September 1, 1968
- Behavioral sensitivity to LSD: Dependency upon the pattern of central 5HT depletion Pharmacology, Biochemistry, and Behavior May 1, 1977
- Central 5-hydroxytryptamine and the effects of hallucinogens and phenobarbital on operant responding in rats. Pharmacology, Biochemistry, and Behavior May 1981
- The effects of d-lysergic acid diethylamide (LSD), 2,5-dimethoxy-4-methylamphetamine (DOM) and d-amphetamine on operant responding in control and 6-hydroxydopamine-treated rats. Pharmacology, Biochemistry, and Behavior November 1980
- The discriminative stimulus properties of 2,5-dimethoxy-4-methylamphetamine (DOM): differentiation from amphetamine. Psychopharmacology 1980