¹Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland

Correspondence: Dr A Czyrak, Institute of Pharmacology, Polish Academy of Sciences, 31-343 Kraków, Smtna Street 12, Poland. Tel: +48 12 662 3253; Fax: +48 12 637 4500; E-mail: czyrak@if-pan.krakow.pl

Received 26 September 2002; Revised 19 December 2002; Accepted 15 January 2003; Published online 9 April 2003.

Abstract

The present study investigated the impact of acute and repeated administrations of corticosterone (10 mg/kg, twice daily, for 7 days) on serotonin (5-HT)_1A receptor function, density and expression. The effect on 5-HT_1A receptor function was assayed in rats by assessing the corticosterone-induced modulation of disruption of prepulse inhibition (PPI) of acoustic startle response induced by 8-OHDPAT, a 5-HT_1A receptor agonist. Our experiments revealed that repeated but not acute treatment with corticosterone attenuated the 8-OHDPAT-evoked disruption of PPI without having any effect on PPI or startle amplitude alone. Chronic corticosterone treatment modulated also the neuronal activity of serotonergic pathways in the brain decreasing the level of 5-HIAA in the raphe nuclei and increasing both 5-HT and 5-HIAA levels in the hippocampus. Nevertheless, the effects of 8-OHDPAT on 5-HT metabolism were not changed by corticosterone. However, 5-HT_1A receptor binding in the ventral hippocampus and entorhinal cortex but not in the raphe nuclei was decreased after chronic corticosterone treatment. It is concluded that chronically elevated corticosterone level is capable of inducing functional desensitization of 5-HT_1A receptors which is paralleled by decreases in the 5-HT_1A receptor binding in the ventral hippocampus and entorhinal cortex, the brain structures shown to be engaged in the regulation of PPI. Alterations in 5-HT_1A receptors may be one of important mechanisms by which glucocorticoids/stress influence various psychiatric conditions.