The sites and mechanisms of action of 2-DI- n-propylamino-5,6-dihydroxytetralin in the hypothalamus of the rat to modify gastric secretion

Abstract

Rats were implanted with chronically indwelling gastric and intracerebral cannulae for the analysis of the hypothalamic sites and mechanisms of action of the dopamine agonist, 2-di- n-propylamino-5,6-dihydroxytetralin, to reduce the volume of gastric secretion and concentration of add. The hypothalamic areas most sensitive to the actions of the tetralin compound to modify gastric secretion were the ventromedial and dorsomedial nuclei. Movement of the injection site 0.5 or 1.0mm away from the ventromedial and dorsomedial nuclei in the anterior, posterior or lateral direction led to reduced effectiveness, or loss of action. In a study restricted to the ventromedial nucleus of the hypothalamus, the tetralin compound (0.1–5μg) was shown to cause dose-dependent changes in gastric secretion, the reduction in concentration of acid being antagonised by the neuroleptic agents, sulpiride, metoclopramide, cis-flupenthixol and haloperidol, and by the α 2-adrenoceptor antagonist, yohimbine injected at the same site. The reduction in secretory volume was antagonised by propranolol. Thus, a locus specificity was shown for the action of the tetralin compound in the dorsomedial and ventromedial hypothalamic nuclei of the rat, to reduce the volume of gastric secretion and concentration of acid. Such actions, as assessed in the ventromedial nucleus, are initiated via neuroleptic-sensitive, dopamine receptor mechanisms with additional involvement of α 2-adrenoceptors in the control of change in concentration of acid, and β-adrenoceptors in the change in volume of secretion.