"Typical and atypical antipsychotics: Role of the Noradrenergic system in the treatment of schizophrenia"

Abstract

We investigated i) effect of antipsychotics on immediate early gene (IEG) and tyrosine hydroxylase (TH) expression in medial prefrontal cortex (mPFC) and locus coeruleus (LC) in rat brain, ii) potential animal model of schizophrenia by conducting prepulse inhibition (PPI) and latent inhibition (LI) studies in genetically modified a??chakragati (ckr)a?? mice, iii) effect of antipsychotic and noradrenergic drugs on the PPI and water maze performance.Risperidone and clozapine, produce greater increases in TH expression in the LC and mPFC. There are immediate as well as delayed dose-dependent effects of olanzapine on patterns of expression. Ckr mice have disrupted LI and PPI. Atypical antipsychotics were more successful in reversing the PPI defects. There was additive effect of alpha1 antagonist, prazosin, and atypical antipsychotics in reversing PPI deficits, in both ckr mice and rats. In rats there was additive effect of alpha2 antagonist, idazoxan, with atypical antipsychotics in improving water maze performance.