Reduction in striatal D2 dopamine receptor mRNA and binding following AF64A lesions

Unilateral lesions by a cholinotoxin, receptor autoradiography, andin situ hybridization techniques were employed to determine if dopaminergic receptors are located on cholinergic interneurons in the caudate-putamen (CPu). Lesion of the CPu with small amounts of the cholinotoxin AF64A resulted in a significant decrease in D₂ receptor mRNA and D₂ receptor binding. The loss was more pronounced in lateral and central portions of the CPu. Results obtained using ³H] SCH23390 binding to D₁ receptors indicated that there was no change in this dopamine receptor subtype in the AF64A-lesioned CPu. A decrease in D₂ receptor mRNA and receptor binding in AF64A-lesioned animals indicates that a population of postsynaptic D₂ receptors is associated with the cholinergic interneurons. Lack of any change in ³H]SCH23390 binding in the AF64A-lesioned animals suggests that D₁ receptors are not located on cholinergic neurons. These results provide evidence to support the selectivity of the lesion when used as indicated.