ANTIPSYCHOTIC-DRUGS INDUCE FOS PROTEIN IN THE THALAMIC PARAVENTRICULAR NUCLEUS - A NOVEL LOCUS OF ANTIPSYCHOTIC DRUG-ACTION

Monitoring expression of c-fos and other immediate-early genes has pro ven a useful method for determining potential sites of action of antip sychotic drugs. Most studies of the effects of antipsychotic drugs on immediate-early gene expression have focused on the basal ganglia and allied cortical regions. We now report that clozapine administration m arkedly increases both the number of cells expressing Fos protein-like immunoreactivity and the amount of Fos protein in the thalamic parave ntricular nucleus, but not the contiguous mediodorsal thalamic nucleus . Comparable doses of several dopamine D-2-like antagonists, including raclopride, sulpiride, remoxipride and haloperidol, did not induce Fo s expression in the paraventricular nucleus. However, loxapine and ver y high doses of haloperidol resulted in a small but significant increa se in paraventricular nucleus Fos expression. The dopamine D-1 recepto r antagonist SCH23390 did not induce Fos in the paraventricular nucleu s or alter the magnitude of the clozapine-elicited increase in Fos exp ression. The serotonergic 5-hydroxytryptamine(2a/2c) antagonist ritans erin, alone or in combination with sulpiride, did not increase Fos exp ression in the paraventricular nucleus. Similarly, the 5-hydroxytrypta mine(2):D-2 antagonist risperidone did not change the amount of Fos pr otein in the paraventricular nucleus. Neither the alpha(1) adrenergic antagonist prazosin nor the muscarinic cholinergic antagonist scopolam ine mimicked the effect of clozapine. The key placement of the paraven tricular nucleus as an interface between the reticular formation and f orebrain dopamine systems suggests that this thalamic nucleus may be a n important part of an extended neural network subserving certain acti ons of antipsychotic drugs.