Intrahypothalamic Injections of Prostaglandins and Prostaglandin Antogonists and Feeding in Sheep

Prostaglandins are thought to play a role in neural transmission, and we have considered the possibility that they may act as feedbacks from fat depots to the central nervous system for maintenance of energy balance. To test for direct prostaglandin effects on the hypothalamus, sheep were implanted with guides directed toward the hypothalamus. With loci in the med'al and anterior hypothalamus in which 1-norepinephrine injections elicited feeding, prostaglandin E1 (14 and 28 nmol) reduced spontaneous feeding for .5 to 1 h. Prostaglandin E2 similarly injected did not affect feeding. Loci in the lateral anterior hypothalamus in which 1-norepinephrine injections did not elicit feeding when injected with prostaglandin El, but not E2, increased feed intake for up to 60 min. Of the prostaglandin antagonists tested (polyphloretin phosphate, oxaprostynoic acid, and SC 19220), only tire first had the predicted effect of increasing feed intake in the loci selected for the l-norepine-phr~ne-bound feeding. Approximately 6 nmol (100 #g) of polyph/oretin phosphate resulted in the maximum response. An injection of 6 nmol of polyphloretin phosphate 30 min before 14 nmol prostaglandin E~ into loci in which 1-norepinephrine elicited feexting resulted in feeding greater than control and much greater than that following carrier and prostaglandin E~ injections. These experiments show that prostaglandin E~, but not Ez, injected into the hypothalamus decreases feeding in medial and anterior loci which show l-norep~nephrine-bound feeding, but it increases