Synergistic interaction of D1 and D2 dopamine receptors in the modulation of the reinforcing effect of brain stimulation.

Rats were trained to press a bar for hypothalamic stimulation, and a frequency-response function was plotted. Quinpirole (a selective D2 agonist) facilitated self-stimulation when injected alone but failed to show the facilitatory effect when injected either 1 hr before or 1 hr after injection of SCH 23390 (a D1 antagonist). Injection of reserpine followed by alpha-methyl-p-tyrosine virtually eliminated self-stimulation. Subsequent injection of either SKF 38393 (a D1 agonist) alone or quinpirole alone did not restore self-stimulation, but a combination of quinpirole and SKF 38393 did. The results suggest that a D2 dopamine agonist facilitates the reinforcing effect of brain stimulation only if D1 receptors are activated by endogenous dopamine or by an exogenous agonist.