The indirect serotonergic agonist d-fenfluramine and prepulse inhibition in healthy men

The specific serotonin (5-HT) releaser, d-fenfluramine (DFEN) was used as a probe of serotonergic effects on prepulse inhibition (PPI). We wished to explore the notion that increased central serotonergic transmission was in part responsible for the psychotomimetic effects of hallucinogens using a relevant and objective physiological measure. Disruption of PPI is considered a valid pharmacological model of some aspects of the behavioural abnormalities in schizophrenia. The aim of this study was to test the hypothesis that increasing central 5-HT neurotransmission with DFEN would produce disruption of PPI. Eighteen healthy male subjects received 45mg of DFEN or placebo in a random order, within-subject, double-blind, and cross-over design. Prepulse to pulse intervals were 30ms and 120ms. The Brief Psychiatric Rating Scale (BPRS) was administered. Although mean PPI at the two prepulse intervals was not significantly different, DFEN prevented the increase in PPI usually seen at the 120ms interval and significantly increased startle magnitude, but did not alter habituation. There were no significant associations between PPI effects and behaviour.