Repeated intermittent administration of psychomotor stimulant drugs altersthe 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 closes. In particular, neuroada ptations within corticolimbic brain structures that mediate incentive learn ing and motivated behavior have been demonstrated after chronic exposure to cocaine, d-amphetamine, and 3,4-methylenedioxymethamphetamine (MDMA). As s timulus-reward learning is likely relevant to addictive behavior (i.e., aug mented conditioned reward and stimulus control of behavior), we have invest igated whether prior repeated administration of psychomotor stimulant drugs of abuse, including cocaine, d-amphetamine, or MDMA, would affect the acqu isition of Pavlovian approach behavior. Methods: Water-deprived rats were tested for the acquisition of Pavlovian a pproach behavior after 5 days treatment with cocaine (15-20 mg/kg once or t wice 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, indi cating accelerated stimulus-reward learning, whereas MDMA administration pr oduced 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 s ensitization can produce long-term alterations in stimulus-reward learning and impulse control that may contribute to the compulsive drug taking that typifies addiction. (C) 2001 Society of Biological Psychiatry.