The reserpine-sensitive dopamine pool mediates (+)-amphetamine-conditioned reward in the place preference paradigm

The neural basis of amphetamine-conditioned reward was investigated in the conditioned place preference paradigm. When bilaterally injected into the nucleus accumbens before the test session, a dopamine receptor blocker, α-flupenthixol, blocked the expression of the amphetamine-conditioned place preference. α-Flupenthixol had no significant effect on spontaneous locomotor activity. Bilateral microinjections of a tyrosine hydroxylase inhibitor, α-methyl-p-tyrosine (α-MPT), decreased (+)-amphetamine locomotor stimulation in a dose-dependent fashion. Two doses of α-MPT that completely blocked (+)-amphetamine locomotor stimulation had no effect on the expression of the conditioned place preference when injected into the nucleus accumbens before testing. Reserpine administered subcutaneously before testing blocked the expression of the conditioned place preference. A dose of reserpine (4.0 mg/kg), which completely blocked the conditioned place preference, did not attenuate (+)-amphetamine-induced locomotor stimulation. This dose of reserpine depleted dopamine in the nucleus accumbens to 4% of its normal value. These data show that (+)-amphetamine-conditioned reward, expressed as a conditioned place preference, is mediated by dopamine release in the nucleus accumbens. Moreover, the dopamine is released from the reserpine sensitive pool, and probably not from the newly synthesized α-MPT-sensitive pool.