Elsevier

Neuroscience

Volume 66, Issue 2, May 1995, Pages 337-346
Neuroscience

Antipsychotic drugs induce Fos protein in the thalamic paraventricular nucleus: a novel locus of antipsychotic drug action

https://doi.org/10.1016/0306-4522(94)00571-LGet rights and content
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Abstract

Monitoring expression of c- fos and other immediate-early genes has proven a useful method for determining potential sites of action of antipsychotic 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 markedly increases both the number of cells expressing Fos protein-like immunoreactivity and the amount of Fos protein in the thalamic paraventricular nucleus, but not the contiguous mediodorsal thalamic nucleus. Comparable doses of several dopamine D2-like antagonists, including raclopride, sulpiride, remoxipride and haloperidol, did not induce Fos expression in the paraventricular nucleus. However, loxapine and very high doses of haloperidol resulted in a small but significant increase in paraventricular nucleus Fos expression. The dopamine D1 receptor antagonist SCH23390 did not induce Fos in the paraventricular nucleus or alter the magnitude of the clozapine-elicited increase in Fos expression. The serotonergic5-hydroxytryptamine2a/2c antagonist ritanserin, alone or in combination with sulpiride, did not increase Fos expression in the paraventricular nucleus. Similarly, the 5-hydroxytryptamine2:D2 antagonist risperidone did not change the amount of Fos protein in the paraventricular nucleus. Neither the α1 adrenergic antagonist prazosin nor the muscarinic cholinergic antagonist scopolamine mimicked the effect of clozapine.

The key placement of the paraventricular nucleus as an interface between the reticular formation and forebrain dopamine systems suggests that this thalamic nucleus may be an important part of an extended neural network subserving certain actions of antipsychotic drugs.

Key words

APD
antipsychotic drug
DA
dopamine
5-HT
5-hydroxytryptamine (serotonin)
-li
-like immunoreactivity
MD
mediodorsal nucleus of the thalamus
NAS
nucleus accumbens
PFC
medial prefrontal cortex
PV
paraventricular nucleus of the thalamus

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