Serotonin involvement in aversive conditioning: reversal of the fear retention deficit by long-term p-chloroamphetamine but not p-chlorophenylalanine.

Drugs that increase serotonin activity—5-MeO-DMT, fenfluramine, and PCA—impair rats' ability to retain fear, as shown by reduced immobility after inescapable shocks. Long-term PCA treatment, which depletes central serotonin neurons, completely blocked the retention impairment caused by acute PCA and fenfluramine, and partially blocked the deficit from 5-MeO-DMT. However, serotonin depletion via PCPA did not block these effects, suggesting different serotonin stores are involved. These findings underscore the role of the ascending serotonin pathway in aversive conditioning in rats.

Study at a glance

Abstract

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a serotonin (5-HT) agonist, fenfluramine and p-chloroamphetamine (PCA), which are 5-HT releasers, produce deficits in fear retention as indicated by a notable lack of the immobility resulting from inescapable shocks. Depletion of central 5-HT neurones after long-term PCA treatment (2 X 10 mg/kg) completely blocked the retention impairment resulting from acute PCA (2.5 mg/kg) and fenfluramine (5 mg/kg), and partially blocked the deficit produced by 5-MeO-DMT (4 mg/kg). 5-HT depletion after p-chlorophenylalanine (PCPA) treatment (200, 100, 100 mg/kg, 72, 48 and 24 h before) did not do so; this is in agreement with other findings which suggest the involvement of different 5-HT stores in the action of PCA and PCPA. These data further underline the importance of the ascending 5-HT pathway in aversive conditioning in the rat.