Corticosterone modulation of somatodendritic 5-HT1A receptor function in mice

Corticosteroid modulation of serotonergic function may play a central role in mood disorders. 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) produces a hypothermia in mice that serves as an in-vivo model of somatodendritic 5-HT1A autoreceptor function. Daily injections (s.c.) of 50 mg/kg of corticosterone (CORT) for 3 days attenuates 8-OH-DPAT hypothermia tested 24 h later. This study sought to further clarify the nature of the CORT-mediated attenuation of somatodendritic 5-HT1A receptor function. Mice underwent various CORT manipulations prior to an 8-OH-DPAT challenge. Neither 14-day bilateral adrenalectomy (ADX), nor CORT 50 mg/kg/day, administered continuously by osmotic minipump over 72 h had any effect on the 8-OH-DPAT hypothermic response. In contrast, daily injections of CORT over three consecutive days caused a significant attenuation in 8-OH-DPAT hypothermia when tested 24 h later. However, administration of an additional dose of CORT 2 h prior to the 8-OH-DPAT challenge occluded this CORT-mediated attenuation in a dose-dependent fashion. The findings demonstrate that CORT modulates somatodendritic 5-HT1A receptor function in a complex manner. Attenuation is seen only after intermittent administration of CORT. In addition, the degree of attenuation depends on CORT concentrations at the time of testing. These findings may have implications regarding mechanisms of adaptation to stress.