CELLULAR-RESPONSES TO PSYCHOMOTOR STIMULANT AND NEUROLEPTIC DRUGS AREABNORMAL IN MICE LACKING THE D1 DOPAMINE-RECEPTOR

Stimulation of dopamine D1 receptors has profound effects on addictive behavior, movement control, and working memory. Many of these functio ns depend on dopaminergic systems in the striatum and D1-D2 dopamine r eceptor synergies have been implicated as well. We show here that dele tion of the D1 dopamine receptor produces a neural phenotype in which amphetamine and cocaine, two addictive psychomotor stimulants, can no longer stimulate neurons in the striatum to express cFos of JunB or to regulate dynorphin. By contrast, haloperidol, a typical neuroleptic t hat acts preferentially at D2-class receptors, remains effective in in ducing catalepsy and striatal Fos/Jun expression in the D1 mutants, an d these behavioral and neural effects can be blocked by D2 dopamine re ceptor agonists. These findings demonstrate that D2 dopamine receptors can function without the enabling role of D1 receptors but that D1 do pamine receptors are essential for the control of gene expression and motor behavior by psychomotor stimulants.