Interactions between Hippocampal Serotonin and the Pituitary-Adrenal Axis in the Septal Driving of Hippocampal Theta-Rhythm

Abstract

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.

Antidepressants Increase Glucocorticoid and Mineralocorticoid Receptor mRNA Expression in Rat Hippocampus in vivo

“…Furthermore, though chronic antidepressant administration may atte nuate corticosterone release to stress [31] (not tested in this study), some [28,29], though not all [23], reports sug gest that even major changes in glucocortioid levels have little effect per se on hippocampal corticosteroid receptor mRNA expression [28,29], Whether the action of antide pressants is mediated directly on hippocampal neurons [11,13,16], or indirectly, as shown by imipramine-induced alterations of GR immunoreactivity in mono amine-containing brain stem nuclei [32], is unknown.…”

“…The hippocampus receives a dense 5-HTinnervation arising from the raphe nuclei [10] which interacts directly with corticosterone-concentrating cells [11]. In dissociated cultures of fetal hippocampal cells increased 5-HT concentrations lead to elevated glu cocorticoid but not mineralocorticoid binding sites [12], However, results in adult animals in vivo have been less clear-cut.…”

Effect of Serotonin Inhibition on Glucocorticoid and Mineralocorticoid Expression in Various Brain Structures

“…Supporting this hypothesis, neurophysiological data demonstrated that lesions of hippocampal serotoninergic inputs with 5,7-DHT directly affect corticosterone-binding neurons [38]and, more recently, Seckl et al [11]showed that MR mRNA expression in CA3 and CA4 hippocampal areas were reduced in a very similar way 21 days after a global lesion of the serotoninergic system compared to a specific lesion of the serotoninergic inputs to the hippocampus. Finally, Mitchell et al [14]observed a direct stimulatory effect of 5-HT on GR-binding sites in hippocampal primary cell cultures.…”

Behavioural and adrenocortical responses to nicotine measured in rats with selective lesions of the 5‐hydroxytryptaminergic fibres innervating the hippocampus

“…The lesion did, however, appear to inhibit the development of tolerance to the effects of nicotine on plasma corticosterone. The data currently available cannot provide an explanation for this observation although it is interesting to note that Azmitia et al (1984) have recently reported that the 5-HTergic fibres which innervate the hippocampus appear to synapse with the neurones which bind corticosterone. These neurones are reported to be involved in the mechanism by which rats terminate the adrenocortical response to a stressful stimulus (Sapolsky et al, 1984).…”