EFFECTS OF A SELECTIVE ALPHA(2)-ADRENOCEPTOR ANTAGONIST, ATIPAMEZOLE,ON HYPOTHALAMIC HISTAMINE AND NORADRENALINE RELEASE IN-VIVO

In vivo microdialysis was used to study the effects of a potent and se lective cu adrenoceptor antagonist, atipamezole, on histamine and nora drenaline release from the medial hypothalamus in anesthetized rats. L ocal perfusion with atipamezole via the microdialysis probe increased histamine release significantly and dose-dependently. However, the eff ect of systemic administration of atipamezole (1 mg/kg) was opposite: it significantly decreased histamine release. Local and systemic admin istration of atipamezole produced an approx. 2-fold increase in noradr enaline release. To study the modulatory effect of noradrenergic neuro ns on histamine release, noradrenaline synthesis was inhibited with al pha-methyl-p-tyrosine. In the microdialysis experiment, rats that rece ived alpha-methyl-p-tyrosine exhibited no decrease, but rather a sligh t increase in histamine release in response to systemic atipamezole ad ministration. These results show clearly that atipamezole enhances nor adrenaline release in vivo from rat hypothalamus and its effects on hi stamine release are dependent on the route of drug administration.