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. Administrations 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 μg/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-dihydroxytryptamine (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 were 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.
Read full abstract