Chronic cocaine administration induces long-term impairment in the drive to obtain natural reinforcers in high- but not low-demanding tasks

Repeated drug exposure induces short- and long-term neuroadaptations in brain reward circuitries that are normally involved in the regulation of motivation. Hence, repeated drug exposure has been suggested to also affect the drive to acquire natural reinforcers. Here, we tested how chronic exposure of rats to cocaine, as well as a subsequent withdrawal period, affects acquisition of natural reinforcers in high- and low-demanding tasks (HD and LD tasks, respectively). We chronically administered cocaine (i.p., 15 mg/kg once daily, or saline in control) for 30 days, followed by a 30-day withdrawal period. We tested the effect of this treatment on the acquisition of two natural appetitive reinforcers, namely self-administering a 10% sucrose solution and mounting a receptive female, under LD and HD conditions. During the cocaine exposure period, behavioral testing took place 18 hours after cocaine injection, namely after the acute pharmacologic effect of the drug dissipated. We show that chronic i.p. cocaine exposure decreased procurement of both reinforcers in HD but not in LD tasks. The effect was observed throughout the administration period with partial recovery after withdrawal. Taken together, we present empirical evidence that chronic exposure to a constant dose of cocaine is sufficient to reduce natural reinforcement, and that this decrease can outlast drug exposure. Importantly, such effects are observed only when high demands are opposing the consumption of the natural reinforcer.