Pharmacological characterization of perifornical hypothalamic beta-adrenergic receptors mediating feeding inhibition in the rat.

This study was designed to characterize pharmacologically the epinephrine-receptive sites, identified in the perifornical lateral hypothalamus, which suppress food consumption in the hungry rat. These sites, studied via direct drug injection into the hypothalamus of freely moving, pargylinepretreated rats with implanted brain cannulae, were sensitive to epinephrine in a dose-dependent, stereochemically specific manner and were also activated by other adrenergic receptor stimulants, with the order of potency being l-epinephrine = l-isoproterenol >dl-salbutamol >dl-terbutaline >l-norepinephrine >l-phenylephrine. The epinephrine-sensitive effects were antagonized by β-adrenergic receptor blockers but not by α-adrenergic blockers. The relative potency of the β-adrenergic antagonists was calculated to be: l-propranolol ? l-alprenolol >dl-butoxamine = l-sotalol = dl-pindolol >l-practolol, with the alpha antagonists phentolamine and tolazoline exhibiting no effect. The receptor antagonism produced by propranolol was stereospecific and reversible by epinephrine. Serotonergic and cholinergic antagonists had little effect. Dopaminergic antagonists, however, were effective in reversing epinephrine's action on feeding. The order of potency of the neuroleptics and structurally related compounds in producing blockade was haloperidol > fluphenazine > chlorpromazine > pimozide > promazine, with the ineffective neuroleptic promethazine and the tricyclic antidepressants imipramine and desipramine having no such effect. These results thus indicate that these hypothalamic epinephrinesensitive sites which inhibit feeding have characteristics expected of classical β-adrenergic receptors, specifically β₂ subtype, and that these sites are closely associated with functionally similar dopaminergic receptors.