Antipsychotics increase microtubule-associated protein 2 mRNA but not spinophilin mRNA in rat hippocampus and cortex.

Antipsychotic (neuroleptic) drugs induce structural alterations in synaptic terminals and changes in the expression of presynaptic protein genes. Whether there are also changes in corresponding postsynaptic (dendritic) markers has not been determined. We describe the effect of 14-day treatment with typical (haloperidol, chlorpromazine) or atypical (clozapine, olanzapine, risperidone) antipsychotics on the expression of two dendritic protein genes, microtubule-associated protein 2 (MAP2) and spinophilin, using in situ hybridization, in the rat hippocampus, retrosplenial, and occipitoparietal cortices. MAP2 mRNA was increased modestly in the dentate gyrus and retrosplenial cortex by chlorpromazine, risperidone, and olanzapine and in the occipitoparietal cortex by chlorpromazine, haloperidol, and risperidone. None of the antipsychotics affected spinophilin mRNA in any area. Overall, these results show a modulation of MAP2 gene expression, likely reflecting functional or structural changes in the dendritic tree in response to some typical and atypical antipsychotics. The lack of change in spinophilin mRNA suggests that dendritic spines are not affected selectively by the drugs. The data provide further evidence that antipsychotics regulate genes involved in synaptic structure and function. Such actions may underlie their long-term effects on neural plasticity in areas of the brain implicated in the pathology of schizophrenia.