Effects of chlorimipramine and lysergic acid diethylamide on efflux of precursor-formed 3-H-serotonin: correlations with serotonergic impulse flow

Abstract

The effects of d-lysergic acid diethylamide (LSD) and chlorimipramine (CIMI) on the firing rate of serotonergic (5-HT) neurons and on the in vivo efflux of 5-HT were investigated in parallel. A cerebroventricular perfusing technique was used to measure the efflux of 3-H-5-HT formed in vivo from 3-H-tryptophan. Impulse flow in serotonergic neurons was monitored by single unit recording from raphe (5-HT) neurons. Doses of LSD and CIMI, which caused a similar degree of inhibition of raphe cell firing, were found to affect 5-HT efflux differently. LSD, at both the 75, and 150 mug/kg doses, produced a similar decrease in 3-H-5-HT efflux. In contrast, CIMI at a low dose (5 mg/kg) did not reduce 5-HT efflux, despite an inhibition in impulse flow. At a high dose (20 mg/kg), CIMI produced an increase in 3-H-5-HT efflux. We conclude that 1) LSD decreased 3-H-5-HT efflux by directly inhibiting impulse flow in 5-HT neurons and/or by a local effect on 5-HT terminals and 2) a low dose of CIMI produces no net change in 3-H-5-HT efflux because a reduction in impulse flow-dependent 5-HT release compensates for blockade by CIMI of 5-HT reuptake.