Impaired DRL 30 performance during amphetamine withdrawal

Repeated administration of psychomotor stimulants may produce an impulsive state that could contribute to the cycle of drug abstinence and relapse seen in human drug addicts. We have previously reported that the inhibitory effects of dopamine (DA) on the firing rate of medial prefrontal cortex (mPFC) neurons were reduced in rats after repeated amphetamine treatment suggesting impaired mPFC DA function. Here, we used a differential reinforcement of low rates of responding (DRL) operant conditioning task, which is dependent on mPFC DA, to test impulsivity and inhibitory control. Food-restricted rats were trained to inhibit a nose poke response for 30s before a subsequent nose poke would result in a food reward (DRL 30). Once training was completed, rats received 5 days of no treatment, daily i.p. saline injections or daily i.p. injections of 5mg/kg amphetamine. Nine days of DRL 30 test performance began following a 3-day withdrawal from treatment. The percent of training active hole nose pokes was significantly increased and the percent of training efficiency was significantly decreased in rats withdrawn from repeated amphetamine administration as compared to saline or naïve rats. This suggests that impulsivity is increased during amphetamine withdrawal, which we hypothesize is associated with disrupted DA function in the mPFC.