Pharmacological characterization of perifornical hypothalamic dopamine receptors mediating feeding inhibition in the rat

Abstract

Mapping studies with central drug injections in the hungry rat have identified the perifornical lateral hypothalamus as being uniquely sensitive to the feeding suppressive effects of exogenous dopamine, as well as anorexic drugs which release endogenous catecholamines. In the present study, the hypothalamic dopamine-receptive sites mediating this phenomenon were pharmacologically characterized. These sites, studied via direct drug injection into the perifornical hypothalamus of freely moving, brain-cannulated rats, were found to be most responsive to dopamine, in a dose-dependent manner, but were also activated by other catecholamine receptor stimulants, with the order of potency being dopamine greater than apomorphine = epinine greater than norepinephrine. Clinically effective neuroleptic compounds antagonized these dopamine-sensitive sites, apparently in a competitive and stereochemically specific manner. The relative potency of the neuroleptics and structurally related compounds was calculated to be haloperidol greater than fluphenazine greater than chlorpromazine greater than pimozide greater than promazine. The ineffective neuroleptic promethazine, the tricyclic antidepressants imipramine and desipramine, and the antagonists of alpha-adrenergic, beta-adrenergic, cholinergic, and serotonergic receptors, did not manifest the ability to reverse dopamine's action. These results thus reveal properties of these hypothalamic dopamine-sensitive, feeding inhibitory sites which match to a large extent the characteristics recently identified for dopamine receptors in the periphery and extrahypothalamic brain areas.