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 phencyclidine 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 phencyclidine or vehicle 24 h prior to behavioral testing following vehicle, 0.5, 2.5 or 5.0 mg/kg amphetamine. Phencyclidine pretreatment significantly increased amphetamine-induced locomotion and rearing in response to 0.5 mg/kg amphetamine. Likewise, phencyclidine pretreatment produced an increase in the number of striatal cells expressing c-Fos following treatment with 0.5 mg/kg amphetamine. Phencyclidine pretreatment did not alter c-Fos induction in the nucleus accumbens, but did decrease the basal number of c-Fos-containing cells in the anterior cingulate cortex. While stereotypy rating revealed that phencyclidine pretreatment enhanced the behavioral response to 5.0 mg/kg amphetamine over time, no other alterations in behavior or c-Fos expression in response to the higher doses of amphetamine were induced by phencyclidine pretreatment. These data demonstrate that the delayed effects of a single dose of phencyclidine alter anterior cingulate cortex neurochemistry, and enhance the behavioral and striatal c-Fos response to a low dose of amphetamine. These findings suggest that the delayed effects of a single dose of phencyclidine may produce a reasonable animal model for schizophrenia.
Turgeon
S M
SM
Department of Psychology, Amherst College, MA 01002, USA.
Roche
J K
JK
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003342:Corpus Striatum / Q000378:metabolism*; D004357:Drug Synergism; D007150:Immunohistochemistry; D008297:Male; D010622:Phencyclidine / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D016760:Proto-Oncogene Proteins c-fos; D000661:Amphetamine; D010622:Phencyclidine