Central 5-hydroxytryptamine and the effects of hallucinogens and phenobarbital on operant responding in rats.
Randall L. Commissaris, William H. Lyness, K E Moore, Richard H. Rech
Pharmacology, biochemistry, and behavior May 1981 DOI: 10.1016/0091-3057(81)90118-0 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled trial Peer reviewed |
|---|---|
| Population | Male rats maintained at 70-80% of their free-feeding weights |
| Interventions | LSD DOM mescaline phenobarbital 5 |
| Dose | LSD 12.5-100 micrograms/kg; DOM 0.125-1.0 mg/kg; mescaline 7.1-14.2 mg/kg; phenobarbital 12.5-50 mg/kg |
| Key findings | Hallucinogens LSD, DOM, and mescaline caused dose-dependent pauses in operant responding, while phenobarbital slowed responding without pausing. After 5,7-dihydroxytryptamine reduced brain serotonin, the dose-response curves for all three hallucinogens shifted left, but phenobarbital's effects were unchanged, suggesting serotonin neurons are involved in hallucinogen behavioral effects but not phenobarbital's. |
Abstract
The present study was designed to examine the role of 5-hydroxytryptamine (5-HT) neurons in the behavioral effects of d-lysergic acid diethylamide (LSD), an indolealkylamine hallucinogen, 2.5-dimethoxy-4-methylamphetamine (DOM) and mescaline, phenethylamine hallucinogens, and phenobarbital, a non-hallucinogen. Male rats, maintained at 70-80% of their free-feeding weights, were trained to press a lever for food pellet reinforcement on a fixed ratio-40 operant schedule. When trained, these rats responded at a constant, rapid rate (approximately 100 responses/min) during daily 40 min test sessions. Administration of hallucinogens caused an abrupt cessation of responding (a "pause"), for some portion of the session. The duration of this pause was dose-dependent for LSD (12.5-100 micrograms/kg), DOM (0.125-1.0 mg/kg) and mescaline (7.1-14.2 mg/kg). On the other hand, phenobarbital (12.5-50 mg/kg) did not cause pausing, but resulted in slowed, erratic intrasession response rates. When the same tests were repeated in rats that had previously received an intracerebroventricular injection of 5,7-dihydroxyptamine (5,7-DHT) the dose-response curves for the pausing induced by all three hallucinogens were shifted to the left, while the behavioral disruption produced by phenobarbital was unaltered. In these animals the 5-HT but not the norepinephrine concentrations was markedly reduced in all brain regions examined. These results suggest that 5-HT neurons are involved with the behavioral effects of hallucinogens but not of phenobarbital.