Stimulation of corticosterone and β-endorphin secretion in the rat by selective 5-HT receptor subtype activation

Changes in plasma concentrations of corticosterone and β-endorphin (β-END) were determined in male rats after treatment with the selective 5-HT_1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) or the non-selective 5-HT agonist 6-chloro-2-(1-piperazinyl)pyrazine (MK-212). The administration of either 8-OH-DPAT or MK-212 increased plasma concentrations of both corticosterone and β-END in a dose-related manner. The corticosterone and β-END responses to 8-OH-DPAT were antagonized by spiperone and (-)-pindolol, both of which have been shown to have high affinity for the 5-HT_1A binding site. In contrast, antagonists which are selective for the 5-HT₂ receptor or non-selective 5-HT antagonists were without effect on the hormone responses to 8-OH-DPAT. The MK-212-induced increase in plasma concentrations of corticosterone and β-END were not affected by treatment with the 5-HT_1A antagonists spiperone and (-)-pindolol. However, the corticosterone and β-END responses to MK-212 were attenuated by the selective 5-HT₂ antagonists ketanserin, ritanserin and altanserin, as well as by the non-selective 5-HT antagonist metergoline. It is concluded that stimulation of either 5-HT_1A or 5-HT₂ receptors results in an activation of the hypothalamic-pituitary-adrenal axis in the rat.