The 5-HT 7 receptor antagonist SB 269970 ameliorates corticosterone-induced alterations in 5-HT 7 receptor-mediated modulation of GABAergic transmission in the rat dorsal raphe nucleus.

RATIONALE: Chronic stress and corticosterone have been shown to affect serotonin (5-HT) neurotransmission; however, the influence of stress on the activity of the dorsal raphe nucleus (DRN), the main source of 5-HT in the forebrain, is not well understood. In particular, it is unknown if and how stress modifies DRN 5-HT7 receptors, which are involved in the modulation of the firing of local inhibitory interneurons responsible for regulating the activity of DRN projection cells.

OBJECTIVES: Our study aimed to investigate the effect of repeated corticosterone injections on the modulation of the inhibitory transmission within the DRN by 5-HT7 receptors and whether it could be reversed by treatment with a 5-HT7 receptor antagonist.

METHODS: Male Wistar rats received corticosterone injections repeated twice daily for 14 days. Spontaneous inhibitory postsynaptic currents (sIPSCs) were then recorded from DRN projection cells in ex vivo slice preparations obtained 24 h after the last injection.

RESULTS: Repeated corticosterone administration resulted in decreased frequency, but not amplitude, of sIPSCs in DRN projection cells. There were no changes in the excitability of these cells; however, corticosterone treatment suppressed the 5-HT7 receptor-mediated increase in sIPSC frequency. Administration of the 5-HT7 receptor antagonist SB 269970 for 7 days beginning on the eighth day of corticosterone treatment reversed the detrimental effects of corticosterone on 5-HT7 receptor reactivity and GABAergic transmission in the DRN.

CONCLUSIONS: Elevated corticosterone level reduces DRN 5HT7 receptor reactivity and decreases GABAergic transmission within the DRN, which can be reversed by the 5-HT7 receptor antagonist SB 269970.