Pharmacological evidence favoring a similarity between alpha adrenoceptors mediating sleep in chicks and cardiac presynaptic alpha-2 receptors in rats
Roach, A.G.; Lefèvre-Borg, F.; Gomeni, R.; Cavero, I.
Journal of Pharmacology and Experimental Therapeutics 222(3): 680-687
1982
ISSN/ISBN: 0022-3565 PMID: 6125585 Document Number: 195982
The .alpha.-adrenoceptors responsible for mediating a sleep-like behavioral state in 2-day-old chicks were characterized pharmacologically. This effect was quantified by measuring the time interval between losing and regaining the righting reflex. In these chicks, i.m. administration of clonidine, guanfacine, oxymetazoline, .alpha.-methyl-norepinephrine and xylazine, in contrast to methoxamine and phenylephrine, produced sleep, the duration of which was dose-dependent. This action was antagonized by yohimbine, rauwolscine (relatively selective .alpha.2-adrenoceptor antagonists) and phentolamine (.alpha.1- and .alpha.2-adrenoceptor antagonists), but not by corynanthine, indoramin, labetalol, prazosin and thymoxamine (relatively selective .alpha.1-adrenoceptor antagonists). The ability of clonidine, guanfacine, oxymetazoline, xylazine and phenylephrine to stimulate cardiac presynaptic .alpha.2-adrenoceptors was assessed in pithed rats in which heart rate was submaximally elevated (.apprx. 70 beats/min) by continuous electrical stimulation of the thoracic segment of the spinal cord. All agonists except phenylephrine reduced this tachycardia, an action that resulted from inhibition of neuronal release of norepinephrine due to activation of presynaptic .alpha.2-adrenoceptors because these compounds did not affect the increase in heart rate evoked by i.v. isoproterenol or norepinephrine. The failure of phenylephrine to modify the neural tachycardia was due neither to a blockade of the neuronal uptake mechanism nor to the stimulation of cardiac .beta.1-adrenoceptors. Only compounds stimulating .alpha.2-adrenoceptors in the rat heart were effective in provoking sleep in young chicks. Because the sedative action of these agents was inhibited by antagonists of .alpha.2- but not .alpha.1-adrenoceptors, it is proposed that the central .alpha.-adrenoceptors mediating sleep in chicks and probably sedation in several species are of the .alpha.2-subtype, like those occurring on sympathetic neurons controlling the rat cardiac pacemaker.