Decreased striatal D1 binding density following mesotelencephalic 6-hydroxydopamine injections: an autoradiographic analysis.

Autoradiographic experiments performed on rats with unilateral mesotelencephalic 6-hydroxydopamine (6-OHDA) injections revealed reduced binding of [3H]SCH23390 to D1 receptors in the striatum ipsilateral to the neurotoxin as well as increased binding of [3H]spiroperidol to D2 receptors in that hemisphere. These opposite influences of injury on the dopamine receptor subtypes occurred in rats sacrificed at 2 weeks or 11 months postoperatively, but neither change was evident at 4 days postoperatively. Equilibrium saturation analysis performed on rats sacrificed at 8 weeks postoperatively indicated that D1 and D2 receptor changes reflected altered Bmax values without KD modifications. Topographic analysis of the D1 decline by quantitative autoradiography revealed that the D1 decrease was greater in dorsal striatum than ventrally. Those striatal regions that showed greater declines in D1 density correspondingly had the greater losses of [3H]mazindol binding after the denervation, suggesting that the decline of D1 binding is a postsynaptic consequence of the reduced mesostriatal dopaminergic innervation. The findings indicate opposite influences of injury on D2 and D1 receptor levels and raise important questions concerning the mechanism by which 6-OHDA injection affects the D1 sites.