The delayed effects of phencyclidine enhance amphetamine-induced behavior and striatal c-Fos expression in the rat

The ability for the delayed effects of phencyclidine to model schizophrenia -like symptomatology was investigated by assessing the effects of phencycli dine pretreatment on amphetamine-induced behavior. Corresponding changes in striatal, nucleus accumbens and anterior cingulate cortex c-Fos induction were also assessed in order to test the hypothesis that alterations in the neurochemistry of these regions accompany phencyclidine-induced changes in amphetamine-induced behaviors. Rats were treated with 15.0 mg/kg phencyclid ine or vehicle 24 h pries to behavioral testing following vehicle, 0.5, 2.5 or 5.0 mg/kg amphetamine. Phencyclidine pretreatment significantly increas ed amphetamine-induced locomotion and rearing in response to 0.5 mg/kg amph etamine. Likewise, phencyclidine pretreatment produced an increase in the n umber of striatal cells expressing c-Fos following treatment with 0.5 mg/ k g amphetamine. Phencyclidine pretreatment did not alter c-Fos induction in the nucleus accumbens, but did decrease the basal number of c-ros-containin g cells in the anterior cingulate cortex. While stereotypy rating revealed that phencyclidine pretreatment enhanced the behavioral response to 5.0 mg/ kg amphetamine over lime, no other alterations in behavior or c-Fos express ion in response to the higher doses of amphetamine were induced by phencycl idine pretreatment. These data demonstrate that the delayed effects of a single dose of phencyc lidine alter anterior cingulate cortex neurochemistry, and enhance the beha vioral and striatal c-Fos response to a low dose of amphe tamine. These fin dings suggest that the delayed effects of a single dose of phencyclidine ma y produce a reasonable animal model for schizophrenia. (C) 1999 IBRO. Publi shed by Elsevier Science Ltd.