D(1) AND D(2) DOPAMINE-RECEPTOR TURNOVER AND D(2) MESSENGER-RNA LEVELS IN THE NEUROLEPTIC-RESPONSIVE AND THE NEUROLEPTIC NONRESPONSIVE LINES OF MICE

The neuroleptic responsive (NR) and neuroleptic nonresponsive (NNR) se lected lines of mice differ significantly in D2 receptor density. By c omparison 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 d egradation were inferred from the repopulation kinetics after N-ethoxy carbonyl-2-ethoxy-1,2 dihydroquinoline administration. The higher D2 r eceptor density in the substantia nigra of the NNR line was associated with an increase in receptor synthesis, with no change in receptor de gradation. As determined by nuclease protection assay, this increase i n receptor synthesis was not associated with an increase in messenger RNA levels. D2 receptor turnover was decreased across the entire rostr al-caudal axis in the lateral caudate-putamen; the decrease in the app arent rate of receptor synthesis was not associated with a change in m essenger RNA levels. By contrast with the decrease in D2 receptor turn over, D1 receptor turnover in the NNR line was significantly increased . Overall, the data suggest that the changes in D2 receptor density co rrelated with the selection of the NR and NNR lines may involve transl ational or post-translational mechanisms.