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 int eractions may be fundamental to the pathophysiology and treatment of depres sive illnesses. It has previously been found that chronic administration of corticosterone leads to adrenal suppression and an attenuation of somatode ndritic 5-HT1A receptor function. Adrenalectomy (ADX) has been shown to cau se an increase in postsynaptic 5-HT1A receptor numbers and possibly functio n. However, other reports have suggested that ADX does not alter somatodend ritic 5-HT1A receptor mRNA or binding, though little is known of the effect of ADX on the function of somatodendritic 5-HT1A receptors. This study inv estigated the effect of markedly reducing corticosterone levels by ADX on 8 -hydroxy-2-(di-12-propylamino) tetralin (8-OH-DPAT)-induced hypothermia in mice, an in vivo model of somatodendritic 5-HT1A receptor function. The deg ree 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-HT1A receptor function, thes e data demonstrate that lowering of corticosteroid levels by ADX have no ef fect. This suggests that the effects of repeated corticosterone administrat ion is not mediated by a secondary adrenal suppression. The difference in t he effects of ADX on somatodendritic as opposed to postsynaptic 5-HT1A rece ptors may reflect the differential expression of corticosteroid receptor su btypes at postsynaptic and somatodendritic sites.