D₁ dopamine receptor agonist-induced fos-like immunoreactivity occurs in basal forebrain and mesopontine tegmentum cholinergic neurons and striatal neurons immunoreactive for neuropeptide Y

The present study sought to determine whether the D₁ dopamine receptor agonist CY 208ndash;243 increases Fos-like immunoreactivity in neurochemically distinct populations of interneurons in the 6-hydroxydopamine-denervated striatum. In vivo microdialysis studies indicate that cholinergic interneurons in the striatum are excited by the administration of CY 208-243 and that this effect is potentiated by dopaminergic deafferentation. Since Fos is considered to be a marker of neuronal activity, we examined the overlap between CY-208-243-induced Fos-like immunoreactivity and striatal cholinergic interneurons labelled with the cholinergic marker enzyme choline acetyltransferase. Unexpectedly, cholinergic interneurons in the striatum were not found to express Fos-like immunoreactivity. However, D₁ agonist-induced Fos-like immunoreactivity was found in neurons immunoreactive for neuropeptide Y. Consequently, the failure of cholinergic neurons in the striatum to express D₁ agonist-induced Fos-like immunoreactivity does not appear to be a general property of striatal interneurons. Indeed, CY 208-243 increased Fos-like 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 has been shown to enhance the release of acetylcholine from their terminals located in the frontal cortex. Thus, unlike cholinergic interneurons in the striatum, the expression of Fos-like immunoreactivity in cholinergic basal forebrain neurons is correlated with an increase in transmitter release. Choline acetyltransferase immunoreactivity was markedly 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 neurons located in the posterior part of the horizontal limb of the diagonal band which included the medial preoptic nucleus. Interestingly, D₁ agonist-induced Fos-like immunoreactivity was located predominantly in those cholinergic neurons which displayed depressed choline acetyltransferase immunoreactivity. Since Fos is often induced as a consequence of increased activity, it is tempting to speculate that those neurons which stained weakly for choline acetyltransferase had been excited by the D₁ agonist administration. Accordingly, the destruction of mesencephalic dopaminergic neurons with 6-hydroxydopamine may have deprived these cholinergic neurons of an excitatory D₁ receptor-mediated drive, resulting in a reduction of choline acetyltransferase immunoreactivity. These results suggest that the degeneration of nigrostriatal dopamine neurons may contribute to the loss of cholinergic basal forebrain function in Parkinson's disease.