Clozapine-induced Fos-protein expression in rat forebrain regions: differential effects of adrenalectomy and corticosterone supplement.

Abstract:

:Unlike classical antipsychotic drugs, clozapine activates the hypothalamo-pituitary-adrenal axis and induces a specific regional pattern of Fos-protein expression in the rat forebrain. Whether corticosterone plays a role in the clozapine-induced Fos response is the subject of this study. Some rats were adrenalectomized and in a number, including intact animals, a corticosterone pellet (100 mg s.c.) was implanted; after 1 week, a single dose of clozapine (20 mg kg(-1) i.p.) was administered. The clozapine-induced Fos response was not affected by adrenalectomy, apart from the nucleus accumbens shell, the subfornical organ and the supraoptic nucleus; there was an increased response in the nucleus accumbens shell, while other regions showed less Fos immunoreactivity. Implantation of the corticosterone pellet in both sham-operated and adrenalectomized animals, reduced the clozapine-induced Fos responses strongly in the hypothalamic paraventricular nucleus, the subfornical organ and possibly in the prefrontal cortex; in the supraoptic nucleus, this effect was seen only in intact animals. The effect of clozapine on plasma corticosterone levels was also diminished by supplemental corticosterone treatment. These results imply that the effects of clozapine are partially dependent upon hypothalamo-pituitary-adrenal axis integrity and activation. The efficacy of clozapine in the treatment of polydipsia and hyponatremia in chronic psychiatric patients may involve clozapine-mediated activation of the cellular activity in the subfornical organ.

journal_name

Eur J Pharmacol

authors

Sebens JB,Middelveld RJ,Koch T,Ter Horst GJ,Korf J

doi

10.1016/s0014-2999(01)00870-6

keywords:

subject

Has Abstract

pub_date

2001-04-06 00:00:00

pages

149-55

issue

1-2

eissn

0014-2999

issn

1879-0712

pii

S0014-2999(01)00870-6

journal_volume

417

pub_type

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