D-1 DOPAMINE-RECEPTOR AGONIST-INDUCED FOS-LIKE IMMUNOREACTIVITY OCCURS IN BASAL FOREBRAIN AND MESOPONTINE TEGMENTUM CHOLINERGIC NEURONS ANDSTRIATAL NEURONS IMMUNOREACTIVE FOR NEUROPEPTIDE-Y

The present study sought to determine whether the D-1 dopamine recepto r agonist CY 208-243 increases Fos-like immunoreactivity in neurochemi cally distinct populations of interneurons in the 6-hydroxydopamine-de nervated striatum. In vivo microdialysis studies indicate that choline rgic interneurons in the striatum are excited by the administration of CY 208-243 and that this effect is potentiated by dopaminergic deaffe rentation. Since Fos is considered to be a marker of neuronal activity , we examined the overlap between CY-208-243-induced Fos-like immunore activity and striatal cholinergic interneurons labelled with the choli nergic marker enzyme choline acetyltransferase. Unexpectedly, choliner gic interneurons in the striatum were not found to express Fos-like im munoreactivity. However, D-1 agonist-induced Fos-like immunoreactivity was found in neurons immunoreactive for neuropeptide Y. Consequently, the failure of cholinergic neurons in the striatum to express D-1 ago nist-induced Fos-like immunoreactivity does not appear to be a general property of striatal interneurons. Indeed, CY 208-243 increased Fos-l ike immunoreactivity in choline-acetyltransferase-positive neurons in the basal forebrain and lateral dorsal tegmental nucleus. In the case of cholinergic basal forebrain neurons, administration of CY 208-243 h as been shown to enhance the release of acetylcholine from their termi nals located in the frontal cortex. Thus, unlike cholinergic interneur ons in the striatum, the expression of Fos-like immunoreactivity in ch olinergic basal forebrain neurons is correlated with an increase in tr ansmitter release. Choline acetyltransferase immunoreactivity was mark edly reduced in cholinergic basal forebrain neurons ipsilateral to the 6-hydroxydopamine lesion. This decrease in choline acetyltransferase immunoreactivity was confined to a pocket of cortically projecting neu rons located in the posterior part of the horizontal limb of the diago nal band which included the medial preoptic nucleus. Interestingly, D- 1 agonist-induced Fos-like immunoreactivity was located predominantly in those cholinergic neurons which displayed depressed choline acetylt ransferase immunoreactivity. Since Fos is often induced as a consequen ce of increased activity, it is tempting to speculate that those neuro ns which stained weakly for choline acetyltransferase had been excited by the D-1 agonist administration. Accordingly, the destruction of me sencephalic dopaminergic neurons with 6-hydroxydopamine may have depri ved these cholinergic neurons of an excitatory D-1 receptor-mediated d rive, resulting in a reduction of choline acetyltransferase immunoreac tivity. These results suggest that the degeneration of nigrostriatal d opamine neurons may contribute to the loss of cholinergic basal forebr ain function in Parkinson's disease.