Influence of substance P on the behavioral changes induced by haloperidol in rats

Locomotor activity and grooming behavior of rats were recorded for a period of 30 min following intraventricular injections of substance P(SP) in doses of 0.60 and 2.50 microgram/rat. The lower dose of the peptide significantly increased locomotion for 10 min and time spent grooming for 25 min. The effects of the same two doses of SP on the hypokinesia induced by various pharmacological treatments modifying catecholaminergic systems were then examined. SP did not affect the behavioral depression produced by alpha-methyl-para-tyrosine (250 mg/kg), FLA-63 (25 mg/kg) and phenoxybenzamine (20 mg/kg). However, SP, in dose of 0.60 microgram/rat, systematically reversed the decrease in locomotor activity induced by a relatively small dose of haloperidol, 0.1 mg/kg. The dame dose of the peptide significantly counteracted the rigidity but not the hypokinesia and catalepsy resulting from the previous administration of a higher dose of haloperidol, 3 mg/kg. The results support the hypothesis that SP may exert direct or indirect function in motor behavior, possible via a modulatory action on brain dopaminergic systems.