MUSCARINIC AND DOPAMINERGIC RECEPTOR SUBTYPES ON STRIATAL CHOLINERGIC INTERNEURONS

Unilateral stereotaxic injection of small amounts of the cholinotoxin, AF64A, caused minimal nonselective tissue damage and resulted in a significant loss of the presynaptic cholinergic markers [H-3]hemicholinium-3 (45% reduction) and choline acetyltransferase (27% reduction). No significant change from control was observed in tyrosine hydroxylase or tryptophan hydroxylase activity; presynaptic neuronal markers for dopamine- and serotonin-containing neurons, respectively. The AF64A lesion resulted in a significant reduction of dopamine D2 receptors as evidenced by a decrease in [H-3]sulpiride binding (42% reduction) and decrease of muscarinic non-M1 receptors as shown by a reduction in [H-3]QNB binding in the presence of 100 nM pirenzepine (36% reduction). Saturation studies revealed that the change in [H-3]sulpiride and [H-3]QNB binding was due to a change in B(max) not K(d). Intrastriatal injection of AF64A failed to alter dopamine D1 or muscarinic M1 receptors labeled with [H-3]SCH23390 and [H-3]pirenzepine, respectively. In addition, no change in [H-3]forskolin-labeled adenylate cyclase was observed. These results demonstrate that a subpopulation of muscarinic receptors (non-M1) are presynaptic on cholinergic interneurons (hence, autoreceptors), and a subpopulation of dopamine D2 receptors are postsynaptic on cholinergic interneurons. Furthermore, dopamine D1, muscarinic M1 and [H-3]forskolin-labeled adenylate cyclase are not localized to striatal cholinergic interneurons.