CHOLECYSTOKININ ALTERATIONS AND EFFECTS OF LEVODOPA ADMINISTRATION INTHE MPTP-TREATED MOUSE-BRAIN

To clarify the effects of levodopa administration on MPTP-induced alte rations in neuropeptides, we examined the effects of repeated levodopa injections (200 mg/kg i.p.) for 2 weeks starting 4 weeks after 1-meth yl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment (30 mg/kg i.p. twice/day for 5 days) on cholecystokinin-octapeptide (CCK-8), substan ce P (SP) and thyrotropin-releasing hormone (TRH) concentrations at 6 weeks after the MPTP treatment. In the striatum, CCK-8 significantly b ut slightly decreased in the MPTP-treated mice, coinciding with the MP TP-induced marked reduction of dopamine (DA). This considerable reduct ion of striatal CCK-8 may result from the selectivity of MPTP since th e 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 C CK-8 level decreased in the thalamus+midbrain, hippocampus and hindbra in of the MPTP + levodopa-treated group, although there were no change s in the MPTP-treated controls. These results suggest that DAergic neu rons, except those in the nigrostriatum, strongly interact with the CC K neurons in these brain regions.