Alterations in the expressions of mRNA for GDNF and its receptors in the ventral midbrain of rats exposed to subchronic phencyclidine

Phencyclidine (PCP) produces schizophrenia-like symptoms in normal humans. This suggests that the dysfunction of glutamatergic neurotransmission may play an important role in the pathology of schizophrenia. However, PCP also exerts its effect on the mesolimbic dopamine (DA) system and modulates DA function in the brain, the abnormality of which is proposed to be a main pathology of schizophrenia. Recently, glial cell-line derived neurotrophic factor (GDNF) has been shown to play a protective role for DA neurons against neurotoxic injuries and maintaining DA function in the brain. We hypothesized that subchronic PCP may alter the function of GDNF in the ventral midbrain, where DA cell bodies are localized. Male Wistar rats were injected intraperitoneally with PCP daily for 10 days at 5 or 10 mg/kg, and their brains were removed 24 h after the last injection. The expressions of GDNF and its receptor (GFRα-1 and c-ret) mRNAs in the substantia nigra compacta (SNC) and ventral tegmental area (VTA) were determined by non-radioactive in situ hybridization, and those of GDNF and c-ret mRNA were found to be increased after the PCP subchronic administration. No significant changes, however, were observed in the expressions of GFRα-1 and basic fibroblast growth factor. These results suggest that subchronic PCP may modulate the function of the GDNF system, which exerts a trophic action on DA neurons in the ventral midbrain.