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Norepinephrine Diffusion from Hypothalamus to Cerebrospinal Fluid and Cerebrospinal Fluid to Hypothalamus of Sheep

Smith Kline Animal Health Products, 1600 Paoli Pike, West Chester, PA 19380
University of Pennsylvania, Philadelphia, PA 19104

ABSTRACT

Although both intraventricular and medial intrahypothalamic injections of adrenoceptor agonists elicited feeding in sheep, it was not clear that the two modes of injection activated similar hypothalamic adrenoceptors. To test the extent of diffusion of cerebroventricular injections, small areas of the hypothalamus 1.5 to 5 mm lateral to the third ventricle in anesthetized sheep were perfused via push-pull cannulas following injection of 480 nmol l-norepinephrine including 2 µCi carbon-14 labeled-dl-norepinephrine into a lateral ventricle. Although fluid from the cisterna magna contained much carbon-14 showing it had passed through the third ventricle, barely detectable amounts were in hypothalamic perfusates. Similarly, 45 nmol carbon-14 labeled carbonate containing 2 µCi injected intraventricularly was not detectable in hypothalamic perfusates. When carbon-14 labeled norepinephrine was injected into hypothalamic tissue, significant amounts of label were in perfusates of the cerebroventricular system. The quantity of norepinephrine diffusing to the cerebrospinal fluid was no more than one-hundredth of that which caused feeding when injected intraventricularly in conscious sheep. The feeding effects of intraventricular and intrahypothalamic injections of l-norepinephrine, therefore, may be mediated by different sets of adrenoceptors.

¹ On leave of absence from the Department of Physiology & Nutrition, University of Leeds, Leeds, United Kingdom.