Cholecystokinin alterations and effects of levodopa administration in the MPTP-treated mouse brain

To clarify the effects of levodopa administration on MPTP-induced alterations in neuropeptides, we examined the effects of repeated levodopa injections (200 mg/kg i.p.) for 2 weeks starting 4 weeks after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment (30 mg/kg i.p. twice/day for 5 days) on cholecystokinin-octapeptide (CCK-8), substance P (SP) and thyrotropin-releasing hormone (TRH) concentrations at 6 weeks after the MPTP treatment. In the striatum, CCK-8 significantly but slightly decreased in the MPTP-treated mice, coinciding with the MPTP-induced marked reduction of dopamine (DA). This considerable reduction of striatal CCK-8 may result from the selectivity of MPTP since the mesolimbic DA neurons coexisting with CCK-8 are intact with the MPTP treatment. Furthermore, this MPTP-induced decrease in CCK-8 persisted with repeated levodopa administration; therefore, the ineffectiveness of the levodopa treatment may have been be due to the degeneration of the nigrostriatal DA neurons. SP and TRH contents showed little or no change with levodopa treatment in the MPTP-treated mouse brain. The CCK-8 level decreased in the thalamus+midbrain, hippocampus and hindbrain of the MPTP+levodopa-treated group, although there were no changes in the MPTP-treated controls. These results suggest that DAergic neurons, except those in the nigrostriatum, strongly interact with the CCK neurons in these brain regions.