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

Chaouloff F(1), Baudrie V, Laude D.

Author information:
(1)Laboratoire de Pharmacologie, INSERM U7, CHU Necker-E. M., Paris, France.

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-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-OH-DPAT. 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-OH-DPAT. 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.

Auteurs Bordeaux Neurocampus