Changes in transcription activity in the rat brain following the acute administration of typical and atypical neuroleptics

Parkinsonism and acute dystonic reactions are extrapyramidal side effects that commonly occur soon after the treatment with typical neuroleptics. A new class of antipsychotic drugs, known as atypical neuroleptics. has shown to have a low incidence of extrapyramidal side effects. The aim of the present study is to estimate the possible differences in activation of transcription complexes in striatal and cortical neurons after acute administration of a typical neuroleptic. haloperidol (HAL) versus an atypical one, olanzapine (OLA). Particulary, we have examined the DNA binding activity and the expression of members of CREB/ATF, AP-1 and NFkB families in nuclear extracts of cortex and striatum of rats receiving either HAL (2 mg/kg), OLA (10 mg/kg). or 0.9% NaCl (control animals). In striatum the acute administration of HAL increases AP-1 binding whereas CREB/ATF and NFkB binding activites show no alterations. In cortex CREB/ATF and NFkB significantly increase after OLA treatment whereas the administration of HAL induces no effects on both striatal and cortical transcription factors. The present results suggest that transcription factor alterations may be correlated with both clinical efficacy and adverse reactions.