Antipsychotic regulation of hippocampal dopamine receptor messenger RNA expression

Abstract

Medial temporal lobe structures including the hippocampus and entorhinal cortex have been implicated in the pathophysiology of schizophrenia. Markers of dopaminergic neurotransmission indicate that these regions receive dopaminergic innervation. Accordingly, dysfunction of dopaminergic neurotransmission within the hippocampus and associated cortical areas may be associated with schizophrenia. Little is known, however, about the expression and regulation of dopamine receptors in these regions. We determined the effects of 14 days of clozapine or haloperidol treatment on dopamine receptor messenger RNA (mRNA) expression in medial temporal regions of the rat brain by in situ hybridization. These two drugs had different effects in the hippocampus and entorhinal cortex, particularly a dissociation of their effects on D2 and D3 receptor mRNA expression. There was a parallel down-regulation of D4 mRNA by both drugs. D1 and D5 transcripts were not regulated by either treatment. These results suggest a differential pattern of regulation of D2-like receptor expression by clozapine and haloperidol in some medial temporal lobe structures. These drugs also appear to cause changes in the expression of these transcripts that differ from what has been reported in the striatum, adding to a growing literature suggesting that hippocampal and striatal dopamine receptors are differentially regulated.