DOPAMINE D1 RECEPTOR MUTANT MICE ARE DEFICIENT IN STRIATAL EXPRESSIONOF DYNORPHIN AND IN DOPAMINE-MEDIATED BEHAVIORAL-RESPONSES

The brain dopaminergic system is a critical modulator of basal ganglia function and plasticity. To investigate the contribution of the dopam ine D1 receptor to this modulation, we have used gene targeting techno logy to generate D1 receptor mutant mice. Histological analyses sugges ted that there are no major changes in general anatomy of the mutant m ouse brains, but indicated that the expression of dynorphin is greatly reduced in the striatum and related regions of the basal ganglia. The mutant mice do not respond to the stimulant and suppressive effects o f D1 receptor agonists and antagonists, respectively, and they exhibit locomotor hyperactivity. These results suggest that the D1 receptor r egulates the neurochemical architecture of the striatum and is critica l for the normal expression of motor activity.