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 [³H]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 [³H]sulpiride binding (42% reduction) and decrease of muscarinic non-M₁ receptors as shown by a reduction in [³H]QNB binding in the presence of 100 nM pirenzepine (36% reduction). Saturation studies revealed that the change in [³H]sulpiride and [³H]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 [³H]SCH23390 and[³H]pirenzepine, respectively. In addition, no change in [³H]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 [³H]forskolin-labeled adenylate cyclase are not localized to striatal cholinergic interneurons.