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 α-methyl-p-tyrosine, conditioned locomotion is not influenced by these treatments. In the present experiment, α-methyl-p-tyrosine (50 mg/kg, s.c.) was give in conjuction with amphetamine (1.5 mg/kg, s.c.) for 8 days before testing for conditioned locomotion. α-Methyl-p-tyrosine completely blocked amphetamine-induce locomotion but only attenuated amphetamine-conditioned locomotion. Reserpine (reduce 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 α-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 conditioned locomotion, but completely blocked amphetamine-conditioned locomotion when given with a α-methyl-p-tyrosine. It is concluded that the α-methyl-p-tyrosine-sensitive pool of dopamine mediates the immediate psychomotor effects of amphetamine, but that both the α-methyl-p-tyrosine- and reserpine-sensitive pools of dopamine are involved in the establishment of amphetamine-conditioned locomotion. In addition, the occurence of amphetamine-conditioned locomotion is independent of the direct effects of amphetamine on locomotion.