D₁ and D₂ dopamine receptor turnover and D₂ messenger RNA levels in the neuroleptic-responsive and the neuroleptic nonresponsive lines of mice

The neuroleptic responsive (NR) and neuroleptic nonresponsive (NNR) selected lines of mice differ significantly in D₂ receptor density. By comparison with the NR line, the NNR line has a lower receptor density in the caudal aspect of the lateral caudate-putamen (-30%) but a higher receptor density in both the substantia nigra ventral tegmental area (+40%). In the present study, the rates of D₂ receptor synthesis and degradation were inferred from the repopulation kinetics after N-ethoxycarbonyl-2-ethoxy-1,2- dihydroquinoline administration. The higher D₂ receptor density in the substantia nigra of the NNR line was associated with an increase in receptor synthesis, with no change in receptor degradation. As determined by nuclease protection assay, this increase in receptor synthesis was not associated with an increase in messenger RNA levels. D₂ receptor turnover was decreased across the entire rostral-caudal axis in the lateral caudate-putamen; the decrease in the apparent rate of receptor synthesis was not associated with a change in messenger RNA levels. By contrast with the decrease in D₂ receptor turnover, D₁ receptor turnover in the NNR line was significantly increased. Overall, the data suggest that the changes in D₂ receptor density correlated with the selection of the NR and NNR lines may involve translational or post- translational mechanisms.