Adrenoceptor antagonists block c-fos response to stress in the mouse brain.

The present study examined the role of monoaminergic systems in mediating the c-fos response to stress in the mouse brain. Mice were pretreated with various monoamine receptor antagonists prior to immobilization stress and were assayed for c-fos immunohistochemically throughout the brain. It was found that the alpha-1 adrenergic antagonist, prazosin significantly reduced the response in 10/12 telencephalic, 2/6 diencephalic and 4/5 brainstem regions and that the beta-1 adrenergic antagonist, betaxolol reduced it in 6/12 telencephalic, 1/6 diencephalic and 015 brainstem regions. The effects of these drugs were not due to nonspecific depressions of neuronal activity as several brain regions with high fos responses were unaffected. Nor were they due to sedation as the drugs did not affect rotorod performance. Neither the brta-2 adrenergic blocker, ICI118,551, the D1/D2 receptor blocker, fluphenazine, the 5HT1A antagonist, WAY 100135, nor the 5HT2 antagonist, ketanserin, produced a clear pattern of effects on the response. It is concluded that of the monoaminergic systems, the noradrenergic is the one most involved in the central fos response to immobilization stress in the mouse brain and that the response is mediated by a mixture of alpha-1 and beta-1 receptors.