Hortnagl_1987_Brain.Res_421_75

The consequences of reduced cholinergic function on noradrenergic and dopaminergic neurons has been studied in various rat brain areas for a period of up to 28 days following bilateral intracerebroventricular infusion of various doses of ethylcholine aziridinium ion (AF64A; 1-5 nmol/ventricle). This treatment resulted in a dose-dependent, persistent decrease in acetylcholine (ACh) content ranging from 50.3 +/- 6.0% to 76.9 +/- 3.8% when compared to vehicle-injected rats. Concomitantly, there was a transient, dose-dependent decrease (up to 46.7 +/- 6.4%) in norepinephrine (NE) levels in hippocampus, cortex and hypothalamus. Whereas the noradrenergic system recovered fully within 28 days after 1-3 nmol AF64A/ventricle, the decrease in NE levels persisted after 5 nmol/ventricle. In striatum, a small decrease in ACh levels 4 days after AF64A infusion was accompanied by a transient, dose-dependent decrease in the levels of dopamine (DA) and its metabolites dihydroxyphenylacetic acid and homovanillic acid, suggesting a decrease in DA synthesis and release. Dopaminergic function was fully restored within 14 days after all doses of AF64A used. These data suggest that reduction of cholinergic function might have a considerable impact on noradrenergic and dopaminergic neurons, causing an increase in NE release as well as depression of dopaminergic function.