Evidence for presynaptic dopamine mechanisms underlying amphetamine-conditioned locomotion.

Rats with a history of receiving (+)-amphetamine in a specific environment exhibit a conditioned psychomotor response when subsequently placed in that environment without drug treatment. Previous work has shown that while the unconditioned effects of amphetamine can be blocked by dopamine D1 or D2 receptor antagonists or with alpha-methyl-p-tyrosine, conditioned locomotion is not influenced by these treatments. In the present experiment, alpha-methyl-p-tyrosine (50 mg/kg, s.c.) was given in conjunction with amphetamine (1.5 mg/kg, s.c.) for 8 days before testing for conditioned locomotion. alpha-Methyl-p-tyrosine completely blocked amphetamine-induced locomotion but only attenuated amphetamine-conditioned locomotion. Reserpine (reduced over the 8 days from 2.5 to 1.25 mg/kg, i.p.) did not block amphetamine-induced locomotion; indeed, potentiation of amphetamine-induced locomotor activity was observed on the last 3 days of treatment. Reserpine treatment in conjunction with alpha-methyl-p-tyrosine treatment blocked amphetamine-induced locomotion for the first 4 days only, with full recovery of amphetamine-induced unconditioned locomotion by the last treatment day. Reserpine alone had no effect on amphetamine-conditioned locomotion, but completely blocked amphetamine-conditioned locomotion when given with alpha-methyl-p-tyrosine. It is concluded that the alpha-methyl-p-tyrosine-sensitive pool of dopamine mediates the immediate psychomotor effects of amphetamine, but that both the alpha-methyl-p-tyrosine- and reserpine-sensitive pools of dopamine are involved in the establishment of amphetamine-conditioned locomotion. In addition, the occurrence of amphetamine-conditioned locomotion is independent of the direct effects of amphetamine on locomotion.