Acute and subchronic MPTP administration differentially affect the serotonergic system in the striatum and prefrontal cortex

Abstract

The principal pathological characteristic of Parkinson’s disease (PD) is the degeneration of dopamine (DA) neurons in the substantia nigra pars compacta. Postmortem studies have also shown reduced levels of basal ganglia serotonin (5-HT), and in vivo studies have reported decreased levels of 5-hydroxy-indolacetic acid. Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) either subchronically (30 mg/kg/day for 5 days) or acutely (20 mg/kg x 4 doses every 2 h) results in varying degrees of striatal DA loss. Current studies determined the effects of these treatment protocols on the serotonergic system. Male C57BL/6J mice were subjected to subchronic and acute MPTP treatment regimen and monoamine levels and motor activity were determined 3 weeks after MPTP treatment. Subchronic and acute MPTP treatment produced 61% and 80% depletion of striatal DA respectively with no decreases in striatal 5-HT. There was a trend towards increases in striatal 5-HT. In the prefrontal cortex (PFC), acute but not subchronic MPTP administration produced significant decreases in 5-HT. PFC dopamine was not changed by either MPTP treatment. Significant decreases in rearing behavior but no changes in locomotor activity were observed. The data suggest that MPTP treatment produces differential effects on striatal monoamine concentrations and motor behavior. Supported by NIH grants S06GM008037 and NS041071.