Effects of adrenalectomy on 8-OH-DPAT induced hypothermia in mice

Complex interactions exist between the hypothalamic-pituitary-adrenal (HPA) axis and the serotonergic system, and it has been suggested that these interactions may be fundamental to the pathophysiology and treatment of depressive illnesses. It has previously been found that chronic administration of corticosterone leads to adrenal suppression and an attenuation of somatodendritic 5-HT_1A receptor function. Adrenalectomy (ADX) has been shown to cause an increase in postsynaptic 5-HT_1A receptor numbers and possibly function. However, other reports have suggested that ADX does not alter somatodendritic 5-HT_1A receptor mRNA or binding, though little is known of the effect of ADX on the function of somatodendritic 5-HT_1A receptors. This study investigated the effect of markedly reducing corticosterone levels by ADX on 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT)-induced hypothermia in mice, an in vivo model of somatodendritic 5-HT_1A receptor function. The degree of 8-OH-DPAT-induced hypothermia did not differ between control, sham, and ADX animals 14 days post operatively. Although repeated administration of corticosterone attenuates somatodendritic 5-HT_1A receptor function, these data demonstrate that lowering of corticosteroid levels by ADX have no effect. This suggests that the effects of repeated corticosterone administration is not mediated by a secondary adrenal suppression. The difference in the effects of ADX on somatodendritic as opposed to postsynaptic 5-HT_1A receptors may reflect the differential expression of corticosteroid receptor subtypes at postsynaptic and somatodendritic sites. Received: 30 March 1998/Final version: 23 July 1998