The role of dopamine in pilocarpine-induced catalepsy

Summary The cataleptic effect of the cholinomimetic compound, pilocarpine, was compared to the pilocarpine-induced changes in striatal dopamine metabolism in rats.Pilocarpine induced catalepsy, the intensity of which increased with increasing dosage, but it did not make rats maximally cataleptic in the doses studied here. Doses higher than 200 mg/kg i.p. could not be studied because of toxicity. Pilocarpine increased the striatal homovanillic acid (HVA) content up to three times the original concentration. The greatest increase was found 2 h after 50 mg/kg of pilocarpine. Atropine (50 mg/kg) antagonized both the catalepsy and HVA increase produced by pilocarpine (200 mg/kg). Apomorphine (10 mg/kg) lowered the striatal HVA content by about 85%. This decrease had disappeared after 4 h. Apomorphine antagonized the HVA increase caused by 50 mg/kg of pilocarpine, but after an initial decrease apomorphine potentiated the HVA increase produced by 200 mg/kg of pilocarpine. Apomorphine did not modify the slight cataleptic effect of 50 mg/kg of pilocarpine but potentiated and prolonged the catalepsy produced by 200 mg/kg of pilocarpine. Pilocarpine-catalepsy was potentiated by -methyl-p-tyrosine (MPT 250 mg/kg) and pilocarpine accelerated the dopamine decrease caused by MPT. Pilocarpine alone in doses up to 200 mg/kg did not statistically significantly change the brain dopamine concentration.These results show that when the striatal cholinergic mechanisms are disturbed changes are induced in striatal dopamine metabolism. The striatal cholinergic and dopaminergic systems are antagonistic but the dopaminergic system can compensate for the overactivity of the striatal cholinergic system only to a certain extent.This study was supported by the National Research Council for Medical Sciences Finland, and the Finnish Medical Society, Duodecim.