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Evidence that 5-HT1A receptors are involved in the adrenaline-releasing effects of 8-OH-DPAT in the conscious rat

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Summary

8-Hydroxy-2-(di-n-propylamino)tetralin (8OH-DPAT) is a 5-HT1A receptor-selective agonist that has recently been reported to trigger adrenal catecholamine release and hyperglycemia. The aim of this study was to analyze in the conscious rat whether the 5-HT1A receptor subtype is involved in these effects.

8-OH-DPAT (0.1–1 mg/kg, i.v.) evoked dose-dependent increases in plasma adrenaline and glucose concentrations. Increases in plasma adrenaline levels peaked 5 min after administration of 8-OH-DPAT; in contrast, plasma glucose levels rose throughout the 20 min period of analysis. Prior administration of (−)pindolol, a beta-adrenoceptor antagonist that blocks 5-HT1A receptors, markedly diminished the rise in plasma adrenaline levels and abolished the hyperglycemia triggered by 8-OHD-PAT. On the other hand, neither the selective beta 1-adrenoceptor antagonist, betaxolol, the selective beta 2-adrenoceptor antagonist, ICI 118.551, nor the 5-HT2 receptor antagonist, ketanserin, affected 8-OH-DPAT-induced increases in plasma adrenaline levels. In addition, except for ICI 118.551 pretreatment, which delayed the hyperglycemic effect of 8-OH-DPAT, none of these antagonists affected the rise in glycaemia evoked by 8-OHD-PAT.

The data suggest that the adrenaline-releasing and a major part of the hyperglycemic effects of 8-OH-DPAT are mediated by activation of 5-HT1A receptors.

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Chaouloff, F., Baudrie, V. & Laude, D. Evidence that 5-HT1A receptors are involved in the adrenaline-releasing effects of 8-OH-DPAT in the conscious rat. Naunyn-Schmiedeberg's Arch Pharmacol 341, 381–384 (1990). https://doi.org/10.1007/BF00180665

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