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-HT1A receptor function.
Adrenalectomy (ADX) has been shown to cause an increase in postsynaptic
5-HT1A receptor numbers and possibly function. However, other reports have suggested that ADX does not alter somatodendritic
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 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-HT1A 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-HT1A 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-HT1A receptors may reflect the differential expression of
corticosteroid receptor subtypes at postsynaptic and somatodendritic sites.