P-CHLOROPHENYLALANINE-INDUCED SEROTONIN DEPLETION - REDUCTION IN EXPLORATORY LOCOMOTION BUT NO OBVIOUS SENSORY-MOTOR DEFICITS

Para-chlorophenylalanine (PCPA) depletes central serotonin (5-hydroxyt ryptamine, 5-HT) by inhibiting tryptophan hydroxylase, an enzyme neces sary for the synthesis of 5-HT. The effects of a wide range of PCPA do ses (150-1000 mg/kg) on spontaneous exploratory locomotor activity in a novel environment, activity in running wheels and a number of sensor y-motor capacities were examined. Administration of 1000 mg/kg PCPA re duced whole brain levels of 5-HT and its metabolite 5-hydroxyindoleace tic acid to 9.4 and 8.2% of control levels, respectively. Treatment wi th PCPA produced a dose-dependent decrease in exploratory locomotion i n an unfamiliar automated open held relative to vehicle-treated animal s. Further, all measures of general, horizontal and vertical activity were suppressed by PCPA treatment. In contrast to previous work, hyper activity of rats chronically housed in cages with running wheel access was not observed. In their home cages, some PCPA-treated rats exhibit ed hyper-reactivity to cutaneous stimulation. No other sensory-motor d eficits were apparent. Previous theories of 5-HT function state that i ts action may be to inhibit motor activity or promote sleep. The prese nt results challenge this view and suggest that 5-HT, at least in cert ain environments, may stimulate locomotor activity without directly co ntrolling various sensory-motor capacities in rats.