Behavioral evidence for the rapid release of CNS serotonin by PCA and fenfluramine

Abstract

Administration of p-chloroamphetamine (PCA) (2.5–10.0 mg/kg) or fenfluramine (FF) (5.0–15.0 mg/kg) to rats induces a behavioral syndrome — consisting of tremor, rigidity, Straub tail, hindlimb abduction, lateral head weaving and reciprocal forepaw treading — which is a reflection of the activity of central serotonin-mediated synapses. The syndrome appears within 3–5 min following i.p. administration of PCA or FF, and the syndrome-inducing effects of PCA and FF are blocked by prior depletion of serotinin with p-chlorophenylalanine. By contrast, the syndrome-inducing effect of 5-methoxy-N,N-dimethyltryptamine (5-M-DMT), which directly stimulates postsynaptic serotonin receptors, is not changed by prior serotonin depletion. Catecholamine depletion with α-methyl-p-tyrosine produces essentially no change in the syndrome-inducing effects of PCA, FF or 5-M-DMT. These data indicate that the initial effect of PCA or FF administration is the rapid functional release of stored serotonin/