D1 and D2 dopamine receptor distribution in the neuroleptic nonresponsive and neuroleptic responsive lines of mice, a...

The present study uses quantitative receptor autoradiography to examine D1 and D2 receptor binding in the neuroleptic responsive and neuroleptic nonresponsive (NNR) lines of mice. The neuroleptic responsive and NNR mice have differed for at least eight generations by an order of magnitude in their sensitivity (ED50s) to catalepsy induced by neuroleptics with a high D2/D1 receptor activity profile. Across the entire rostral-caudal dimensions of the lateral caudate-putamen (CPu), of the dorsomedial CPu, the nucleus accumbens and substantia nigra zona reticulata, we found no difference in the density of [3H]SCH 23390 binding sites. [3H]Spiroperidol binding sites were not different in the dorsomedial CPu or nucleus accumbens but were significantly decreased (20-30%) in the NNR line in the caudal aspect of the lateral CPu. The NNR line also showed a significant elevation of D2 autoreceptors across all the midbrain dopamine cell groups (A8, A9 and A10); the increases ranged from 20 to 50%. Overall, the data show that selection of mice for response and nonresponse to neuroleptic-induced catalepsy is associated with significant changes in D2 but not D1 receptor density.