Effects of repeated treatment with amphetamine or phencyclidine on working memory in the rat

Repeated exposure to psychomotor stimulants produces long-lasting molecular, cellular and locomotor behavioral changes. Such changes are likely to contribute to the development of drug addiction and psychosis. It is not clear whether these durable changes are accompanied by lasting changes in cognition. We examined the long-term effects of repeated treatment with phencyclidine (PCP) or amphetamine on working memory, using a discrete, paired-trials, delayed-alternation task sensitive to the acute effects of PCP and amphetamine, and to the integrity of the prefrontal cortex. Twice daily treatment with PCP (5.0 mg/kg) or amphetamine (2.5 mg/kg) for 5 days did not produce lasting, significant impairments in alternation performance in comparison to either pre-treatment baseline performance or to the vehicle-treated group. Subsequent challenge doses of PCP (1, 3 and 5 mg/kg) produced alternation deficits in vehicle, PCP, and amphetamine pre-treated groups that were dependent on dose, but not on pre-treatment regimen. However, rats pre-treated with PCP showed a trend towards sensitization in response to PCP challenge. The present data suggest that psychostimulant treatment regimens that are reported to produce long-lasting changes in neural morphology and locomotor behavior may not produce equally durable changes in working memory.