The involvement of dopamine D1 and D2 receptors in the locomotor stimulation produced by (+)-amphetamine in naive and dopamine-depleted mice.

The interaction between (+)-amphetamine and dopamine (DA) D1 and D2 receptors was investigated. In naïve mice, i.e., mice with intact stores of DA, both the selective D1 antagonist SCH23390 and the selective D2 antagonist spiperone blocked the locomoter stimulation produced by (+)-amphetamine. The selective D1 agonist SKF38393 (6 mg/kg intraperitoneally) did not produce a consistent dose-dependent effect on the response to (+)-amphetamine in naïve mice. In mice depleted of DA with reserpine 24 hr before a challenge with (+)-amphetamine, neither SCH23390 nor spiperone were completely effective in blocking (+)-amphetamine. A combination of spiperone plus SCH23390 was, however, more effective than either drug alone, although significant activity remained even after the combination. In mice pretreated with reserpine and various doses of alpha methyl-p-tyrosine (alpha MPT, intraperitoneally), the degree of stimulation produced by (+)-amphetamine was dependent on the amount and frequency of alpha MPT dosage - the higher and more frequent the dose, the more effective the blockade. In these animals, both SKF38393 and the selective D2 agonist quinpirole potentiated the stimulation induced by (+)-amphetamine when the dose of alpha MPT was not maximal. However, in those animals pretreated with reserpine plus two doses each of 400 mg/kg alpha MPT, neither SKF38393 nor quinpirole were effective in potentiating (+)-amphetamine. Nevertheless, when SKF38393 and quinpirole were administered simultaneously to these mice, marked locomotor stimulation occurred implying that the pretreatment itself had not rendered the mice incapable of locomotion.(ABSTRACT TRUNCATED AT 250 WORDS)