Moderate differences in circulating corticosterone alter receptor-mediated regulation of 5-hydroxytryptamine neuronal activity

Circulating glucocorticoid Levels vary with stress and psychiatric illness and play a potentially important rote in regulating transmitter systems that regulate mood. To determine whether chronic variation in corticosterone levels within the normal diurnal range altered the control of 5-hydroxytryptamine (5-HT) neuronal activity, mate rats were adrenalectomized and implanted with either a 2% or 70% corticosterone/cholesterol pellet (100 mg). Two weeks Later, the regulation of 5-HT neuronal activity in the dorsal raphe nucleus was studied by in vitro electrophysiology. At this time, serum corticosterone levels approximated the Low-point (2%) and mid-point (70%) of the diurnal range. The excitatory response of 5-HT neurones to the alpha(1)-adrenoceptor agonist phenylephrine (1-11 muM) was significantly greater in the 2% group compared to the 70% group. By contrast, the inhibitory response to 5-HT (10-50 muM) was significantly Lower in the 2% group compared to the 70% group. Thus, chronic variation in circulating corticosterone over a narrow part of the normal diurnal range causes a shift in the balance of positive and negative regulation of 5-HT neurones, with increased alpha(1)-adrenoceptor-mediated excitation and reduced 5-HT-mediated autoinhibition at tower corticosterone levels. This shift would have a major impact on control of 5-HT neuronal activity.