Ascorbate potentiates amphetamine-induced conditioned place preference and forebrain dopamine release in rats.

In order to evaluate the effects of ascorbate, which is known to modulate dopamine neurotransmission, on the reinforcing effects of amphetamine, we coadministered ascorbate and amphetamine during the acquisition of conditioned place preference (CPP) in rats. Our results indicate that 100 mg/kg ascorbate potentiates the CPP induced by 0.5 mg/kg, but not 1.0 mg/kg, amphetamine. A higher dose of ascorbate (500 mg/kg) did not influence the CPP induced by either dose of amphetamine. In vitro release assays revealed that, whereas ascorbate alone (0.01-1.0 mM) did not influence striatal dopamine levels, this vitamin potentiated amphetamine-induced dopamine release in both the nucleus accumbens and neostriatum. Collectively, these results raise the possibility that ascorbate potentiates amphetamine-induced CPP by increasing the ability of this psychostimulant to release dopamine.