The effects of centrally acting adrenergic agonists on temperature and on explorative and motor behaviour. Relation with effects on quasi-morphine withdrawal behaviour

Seven structurally unrelated adrenergic agonists were compared in three models to measure sedation viz. hole-board exploration, open-field activity and rotarod performance. It appeared that all compounds exerted the same order of potency in these models except for BHT-920 which was more active in the open-field. The other compounds were clonidine, azepexole, guanfacine, lofexidine, UK-14.304 and ST-587. The sedative effect appeared to be not causally related with the hypothermic activity since much higher doses were necessary for the latter effect. There was a relation between the sedative effects and the suppression of body shakes and enhanced locomotor activity induced by dipropylacetate, a potent model for morphine-withdrawal behaviour. The body shakes appeared to be more sensitive than locomotor activity suggesting that the antiwithdrawal action of Alpha 2-agonists might be intrinsically higher than their sedative action. The data support earlier findings indicating that the antiwithdrawal action of clonidine is mediated by Alpha 2-adrenoceptors.