Acute administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) reduces dopamine and serotonin but accelerates norepinephrine metabolism in the rat brain. Effect of chronic pretreatment with MPTP.

Acute administration of MPTP (a synthetic heroin substitute) at 10-30 mg/kg (s.c.) produced 'Straub tail' phenomena, piloerection and reduced pelvis elevation in rats. The same dose decreased the concentrations of dopamine metabolites and reduced the rate of dopamine synthesis in the striatum. MPTP also reduced the metabolism of serotonin but accelerated that of norepinephrine in their corresponding terminal areas. The effects on central monoamines probably were not due to an agonistic action of MPTP on dopaminergic and serotonergic receptors, since MPTP only exhibited micromolar affinity to the corresponding binding sites. Furthermore, MPTP failed to induce rotational behavior in animals with unilateral nigrostriatal lesions. Chronic treatment of rats with MPTP (10 mg/kg s.c., daily for 3 weeks) did not result in massive degenerative changes in the nigrostriatal system. Histochemical analysis showed intact dopaminergic neurons. Striatal dopamine levels only were reduced by 10%. Dopaminergic neurons in rats chronically treated with MPTP responded normally to a pharmacological stimulus increasing their transmitter synthesis. Chronic treatment did not affect their response to an acute injection of MPTP.