DOPAMINE D3 RECEPTOR MUTANT MICE EXHIBIT INCREASED BEHAVIORAL SENSITIVITY TO CONCURRENT STIMULATION OF D1 AND D2 RECEPTORS

The dopamine D3 receptor is expressed primarily in regions of the brai n that are thought to influence motivation and motor functions. To spe cify in vivo D3 receptor function, we generated mutant mice lacking th is receptor. Our analysis indicates that in a novel environment, D3 mu tant mice are transiently more active than wild-type mice, an effect n ot associated with anxiety state. Moreover, D3 mutant mice exhibit enh anced behavioral sensitivity to combined injections of D1 and D2 class receptor agonists, cocaine and amphetamine. However, the combined ele ctrophysiological effects of the same D1 and D2 agonists on single neu rons within the nucleus accumbens were not altered by the D3 receptor mutation. We conclude that one function of the D3 receptor is to modul ate behaviors by inhibiting the cooperative effects of postsynaptic D1 and other D2 class receptors at systems level.