Effect of serotonin depletion by p-chlorophenylalanine upon discriminative behaviours

1. Para-chlorophenylalanine (p-CPA), a competitive inhibitor of the serotonin (5-HT) synthesis enzyme tryptophan hydroxylase, was administered to rats at a dosage (100 mg/kg daily for 3 days) that depletes 5-HT. 2. Different groups of these rats were previously trained to discriminate the interoceptive stimuli produced by amphetamine, cathinone, 3,4-methylenedioxymethamphetamine (MDMA), N-ethyl-3,4-methylenedioxyamphetamine (MDE), fenfluramine or yohimbine, and the effect of p-CPA pretreatment upon their discriminative performance was compared with the effect of saline (control) pretreatment. 3. p-CPA was shown to have no effect upon the dopaminergically-mediated stimuli produced by the stimulants amphetamine and cathinone or upon yohimbine performance. 4. p-CPA significantly decreased discriminative performance with the serotonergic releasing drugs MDMA, MDE and fenfluramine. This decrease in discriminative performance returned to pre-p-CPA (criterion) levels at a time (9-12 days) when 5-HT has been reported to replete to normal brain concentrations. 5. It is concluded that p-CPA pretreatment lowers brain 5-HT and, in turn, significantly decreases the ability of rats to discriminate centrally active drugs whose interoceptive cueing stimuli are mediated by 5-HT neurons.