Interactions between hippocampal serotonin and the pituitary-adrenal axis in the septal driving of hippocampal theta-rhythm.

Stimulation of the septal area at a frequency between 6 and 10 Hz is able to drive hippocampal theta. In freely moving male rats, the minimum threshold current for driving theta occurs at 7.7 Hz. Disruption of the pituitary-adrenal axis by injection of corticosterone to normal rats or by bilateral adrenalectomy (ADX) causes a shift of the minimum theta-driving threshold to 6.9 Hz. Corticosterone injection to ADX rats returns the minimum to 7.7 Hz. Specific and localized removal of hippocampal serotonergic fibers by intracerebral injections of 5,7-dihydroxytryptamine (5,7-DHT) produces the same shift to a 6.9-Hz minimum threshold as does corticosterone or ADX. We further report that these effects of manipulating the adrenocortical and serotonergic systems act through related (or common) mechanisms since: (1) 5,7-DHT shift to 6.9 Hz can be reversed to 7.7 Hz by injection of corticosterone; (2) 5,7-DHT lesions in an ADX rat produce a normal theta threshold minimum at 7.7 Hz, and (3) in a combined ADX- and 5,7-DHT-lesioned rat, corticosterone again produces a 6.9-Hz minimum as this hormone does in normal rats. These results suggest that the serotonergic inputs to the hippocampus interact with the same neurons which concentrate corticosterone.