Inhibition of dopamine efflux in the rat nucleus accumbens during abstinence after free access to d-amphetamine.

Abstinence following 'binge' use of psychostimulants is hypothesized to be related to a depletion of synaptic dopamine (DA) in the nucleus accumbens. The present study, therefore, tested the pharmacological responsiveness of the mesolimbic DA system to d-amphetamine injections, measured by in vivo chronoamperometry with stearate-modified graphite paste electrodes, during voluntary abstinence when rats were given prolonged free availability to d-amphetamine. Rats self-administered i.v. d-amphetamine (FR-1 time out 30 s; 0.25 mg/kg per inf) in three sessions, each separated by approximately 24 h, (1) to a criterion of 12 infusions; (2) for 24 h and (3) for 48 h. During the third session, when self-administration had ceased for at least 1.5 h (abstinence), and DA levels were near, or below, pre-drug baseline values, rats received passive i.v. injections of d-amphetamine or vehicle in a pattern that mimicked self-administration patterns during the first hour of the 48 h session. In contrast to the significant increases in DA efflux observed during the first hour of self-administration, d-amphetamine injections during abstinence did not increase DA oxidation currents. Furthermore, the length of the abstinence period was correlated with the time required for DA to return to pre-abstinence values. Together, these results suggest that the mesolimbic DA system is pharmacologically unresponsive to the actions of d-amphetamine during abstinence, and that resumption of drug use is associated with 'recovery of function' in the mesolimbic DA system.