Alterations of somatostatin and its modulation by levodopa in MPTP-treated mouse brain

We examined the changes in the concentrations of neuropeptides in various regions of the mouse brain 1, 2 or 6 weeks after 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) treatment (30 mg/kg i.p. twice/day for 5 days) and further examined the effects of levodopa injections (200 mg/kg i.p.) for 14 days starting 4 weeks after MPTP treatment on regional somatostatin (SRIF) concentrations. Substance P, cholecystokinin-octapeptide and thyrotropin-releasing hormone did not show any significant changes up to 6 weeks after MPTP treatment, whereas the SRIF concentration increased 1 week after MPTP treatment but decreased thereafter, showing a marked decrease in the striatum and hippocampus after 6 weeks. In the striatum, the decreased concentration of SRIF recovered to the normal level with levodopa injections. This SRIF depletion could be a change secondary to dopamine depletion. On the other hand, in the cerebral cortex, while showing no change in the SRIF concentration after MPTP treatment, the concentration decreased significantly with levodopa injections. In the hippocampus, the decreased SRIF levels were still low after levodopa treatment. Since it has been reported that SRIF concentrations are significantly reduced in the frontal cortex and hippocampus of demented parkinsonians and patients with senile dementia of the Alzheimer type and that levodopa treatment induced various psychiatric side effects, the results of the present study suggest some relationship among levodopa treatment, SRIF depletion and the demented state.