Brain adrenergic system in the feeding response induced by 2-deoxy-D-glucose.

Brain adrenergic system in the feeding response induced by Z-deoxy-D-glucose. Am. J. Physiol. 223(4) : 945-950. 1972.-A reliable eating response was obtained in rats on injection of the glucose analogue, 2-deoxy-n-glucose (Z-DG; 750 " g/kg, ip), which produces decreased intracellular glucose utilization of most tissues and particularly of brain. Intraventricular administration of an a-adrenergic blocking agent, phentolamine (50 and 10 pg), given concomitantly with 2-DG, greatly reduced the eating response to the latter, while propranolol (100 pg), a P-adrenolytic drug, administered by the same route, was ineffective. At the doses used, neither drug affected basal food consumption. Similarly to phentol-amine, central administration of another cr-adrenergic blocker, azapetine (50 pg), reduced the 2-DG action, while MJ-1999 (100 A%), a P-a cl renergic blocker, like propranolol had no effect. The increased food intake due to 2-DG was also inhibited by sys-temic administration of ar-methyl-p-tyrosine (50 mg/kg), an inhibitor of catecholamine synthesis, and by the chemical sym-pathectomy due to central administration of 6-hydroxydopamine. The results provide evidence for the hypothesis that cr-adrenergic modulation of postsynaptic activity by norepinephrine is involved in the neural control of the feeding response elicited by the in-sufficiency of metabolizable glucose. feeding behavior; central glucoprivation; blocking agents; W-methyl-p-tyrosine; 6-hydroxydopamine; glucoprivic control of feeding A LARGE AND FAIRLY CONSISTENT body of evidence has been collected showing that in mammals the eating response is mediated by neuronal adrenergic receptors (15, 16, 25). Feeding is said to be facilitated by neurons ascending in the lateral hypothalamus via the medial forebrain bundle to form noradrenergic' synapses in the diencephalon and forebrain (3, 13). E p x erimental proof has also been presented , however, suggesting that adrenergic synapses in the hypothalamus mediate satiety rather than feeding; for instance, from experiments involving the direct application of norepinephrine (NE) to the perifornical region of the medial forebrain bundle (23). Recently Smith and Epstein (29) have shown that the analogue of glucose, 2-deoxy-n-glucose (2DG), a specific inhibitor of intracellular glucose utilization (7), induces increased food intake in monkeys and rats as a result of cerebral glucoprivation. In the light of the mentioned controversy on the role played by brain catecholamines in the eating response, it seemed of interest to investigate whether or not 2DG-induced hyperphagia required the integrity of the adrenergic system. Therefore, in the work to be reported, the effect of the pharmacological interruption of cerebral nor-adrenergic transmission on the feeding response elicited by the …