Repeated intermittent administration of psychomotor stimulant drugs alters the acquisition of Pavlovian approach behavior in rats: differential effects of cocaine, d-amphetamine and 3,4-methylenedioxymethamphetamine (“ecstasy”)

Background: Psychomotor stimulant drugs can produce long-lasting changes in neurochemistry and behavior after multiple doses. In particular, neuroadaptations within corticolimbic brain structures that mediate incentive learning and motivated behavior have been demonstrated after chronic exposure to cocaine, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). As stimulus–reward learning is likely relevant to addictive behavior (i.e., augmented conditioned reward and stimulus control of behavior), we have investigated whether prior repeated administration of psychomotor stimulant drugs of abuse, including cocaine, d-amphetamine, or MDMA, would affect the acquisition of Pavlovian approach behavior. Methods: Water-deprived rats were tested for the acquisition of Pavlovian approach behavior after 5 days treatment with cocaine (15–20 mg/kg once or twice daily), d-amphetamine (2.5 mg/kg once or twice daily), or MDMA (2.5 mg/kg twice daily) followed by a 7-day, drug-free period. Results: Prior repeated treatment with cocaine or d-amphetamine produced a significant enhancement of acquisition of Pavlovian approach behavior, indicating accelerated stimulus–reward learning, whereas MDMA administration produced increased inappropriate responding, indicating impulsivity. Abnormal drug-induced approach behavior was found to persist throughout the testing period. Conclusions: These studies demonstrate that psychomotor stimulant-induced sensitization can produce long-term alterations in stimulus–reward learning and impulse control that may contribute to the compulsive drug taking that typifies addiction.