Lack of effects of typical and atypical antipsychotics in DARPP-32 and NCS-1 levels in PC12 cells overexpressing NCS-1

We chronically treated both PC12 WT and PC12 Clone cells with typical (Haloperidol) or atypical (Clozapine and Risperidone) antipsychotics for 14 days. Using western blot technique we observed that there is no change in NCS-1 and DARPP-32 protein levels in both PC12 WT and PC12 Clone cells after typical and atypical antipsychotic treatments.Because we observed no alteration in NCS-1 and DARPP-32 levels in both PC12 WT and Clone cells treated with typical or atypical antipsychotics, we suggest that the alteration in levels of both proteins in schizophrenic's PFC is related to psychopathology but not with antipsychotic treatment.Schizophrenia is the major psychiatry disorder with prevalence of approximately 1% of worldwide population [1]. It is characterized by psychosis, apathy and social withdrawal, and cognitive impairment, which results in altered functioning in many aspects of life. It is a life-long disorder and, although exact disease cause remains unknown, it is known that the disease can be triggered by a combination of genetic and environmental factors [2].It is well known that dopamine-mediated neurotransmission imbalance is associated with schizophrenia [3-5] and several studies have demonstrated altered activity of prefrontal cortex (PFC) of schizophrenics during hallucinations, delusions and cognitive tests [6-8]. Recent studies have demonstrated change in the expression of two proteins involved with dopaminergic signaling modulation in the schizophrenics PFC [9-11]. It was reported decrease of dopamine and cyclic adenosine 3':5'-monophosphate-regulated phosphoprotein of relative molecular mass 32,000 (DARPP-32) and upregulation of Neuronal Calcium Sensor-1 (NCS-1) expression [12,13].Dopamine receptors are G protein-coupled receptors classified into two subtypes: D1-like receptor subtypes (D1, D5), positively coupled to adenylyl cyclase (Gs), and D2-like receptor subtypes (D2, D3, D4), negatively coupled to adenylyl cyclase (Gi) [14]. D1 receptor subtype