Differential expression of Homer 1 gene by acute and chronic administration of antipsychotics and dopamine transporter inhibitors in the rat forebrain

Abstract

Neuronal expression of immediate-early genes in response to a drug is a powerful screening tool for dissecting anatomical and functional brain circuitry affected by psychoactive compounds. We examined the effect of dopaminergic perturbation on two Homer 1 gene splice variants, Homer 1a and ania-3, in rat forebrain. Rats were treated with the "typical" antipsychotic haloperidol, the "atypical" quetiapine, or the selective dopamine transporter (DAT) inhibitor GBR 12909 in acute and chronic paradigms. Our results show that the high affinity dopamine D(2) receptor antagonist haloperidol strongly induces Homer 1 gene expression in the caudate-putamen, whereas quetiapine, a fast D2R dissociating antagonist, does not. This confirms that Homer 1 may be considered a predictor of "atypicality" of antipsychotic compounds in acute and also chronic regimens. Chronic treatment with GBR 12909 showed a strong induction in the parietal cortex, resembling the activation of "sensitization" circuitry by stimulants. Finally, we describe a differential spatial induction pattern of Homer 1 gene within the caudate-putamen by typical antipsychotics and DAT blockers, and propose a novel method to quantitate it.