Immunohistochemistry of c-Fos protein was performed to study changes in neuronal activity in discrete brain areas of mice repeatedly treated with phencyclidine (PCP) showing enhancement of immobility in the forced swimming test, this behavioral change being considered as avolition, which is one of negative symptoms of schizophrenia. Repeated treatment with PCP significantly prolonged immobility time in the forced swimming test, compared with saline treatment. The c-Fos protein expression of mice showing PCP-induced enhancement of immobility was increased in certain brain regions, such as the retrosplenial cortex, pyriform cortices, pontine nuclei, cingulate, frontal cortex and thalamus, compared with that of PCP-treated, non-swimming and saline-treated, swimming groups. These results suggest that increased c-Fos protein is involved in the expression of PCP-induced enhancement of immobility, and c-Fos expression plays a role in negative symptoms-like behavioral changes.
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