Pharmacology Biochemistry & Behavior, Vol. 15, pp. 735-738, 1981. Printed in the U.S.A. The Effect of Prostaglandins (PGE2 and PGF2 ) on Food Intake in Rats ALLEN S. LEVINE AND JOHN E. MORLEY Neuroendocrine Research Laborator3,, Minneapolis VA Medical Center, Minneapolis, MN 55417 and Division of Endocrinology, Departments of Medicine and Food Science and Nutrition University of Minnesota, Minneapolis and St. Paul Received 15 April 1981 LEVINE, A. S. AND J. E. MORLEY. The efJ~ct of prostaglandins (PGE2and PGF2~)onjood intake in rats. PHARMAC. BIOCHEM. BEHAV. 15(5) 735-738, 1981.--Intracerebroventricular administration of PGF2~and PGE~ suppressed food intake in several feeding models. PGF2, (20/xg) and PGE2 (20/xg to 1 /xg) suppressed food intake following a 24 hour starvation. PGFz~ (20/xg) and PGEz (20/xg) suppressed food intake following central administration of the feeding induces norepinephrine and muscimol. These prostaglandins also suppressed stress induced eating using the tail pinch model at doses of 20/zg, 10/xg and 5/xg with eating returning to control levels at the 1/xg dose. D-Ala Methionine Enkephalin failed to alter the suppressive effects of PGF2~ and PGE2 at a dose of 1/xg but successfully reversed the effect of PGF2~ at a 10 txg dose while still having no effect on PGE~ suppression of feeding. Prostaglandins Food intake Stress induced eating Tail pinch PROSTAGLANDINS are ubiquitously distributed through- out the body and are synthesized from fatty acid precursors by various tissues including brain [6,7]. In 1964, Horton re- ported that prostaglandins of the E series decreased feeding in starved cats after intracerebroventricular injection [18]. Subsequently, Baile and co-workers demonstrated that a variety of prostaglandins (E,, E2, E,,, Ez,, A,, B0 decreased feeding in the rat (after parenteral and/or intrahypothalamic injections [4,32]) and in sheep after intrahypothalamic injec- tions [3]. Doggett and Jawaharlai [10] demonstrated that a number of prostaglandin precursors inhibit food intake in the rat and this anorexia can be reversed by indomethacin. Re- cently, PGBx, an oligomeric derivative of prostaglandin BI has been shown to decrease appetite and to normalize weight and blood glucose in hereditary diabetic mice [31]. Prosta- glandins produce their anorectic activity without producing behavioural depressant effe,cts [4]. The anorectic effect is not related to changes in temperature since the satiety effect is seen after administration of prostaglandins that produce either hypo- or hyperthermia [4,10]. Also Doggett and Jawaharlal [10] showed that the anorexia is not due to pain or irritative properties of prostaglandin injections since induc- tion of comparable pain with 3% acetic acid did not affect food intake in rats deprived of food for 22 hours. PGE, has been shown to be effective at reducing food intake when injected into the lateral hypothalamic and anterior com- misural, but not in the perifornical hypothalamic area [4]. In sheep, PGE, has a dual action on food intake; reducing feed- ing when injected in sites in the hypothalamus where norepi- nephrine induces feeding and eliciting feeding in the lateral hypothalamic,/3-adreno-receptor sensitive areas [3]. Baile et al. [4] have suggested that the prostaglandins may be components of a signal relating fat depots and energy balance regulation. They hypothesized that prostaglandins produced in adipose tissue acts on hypothalamic centers to modulate long term control of feeding and thus play a role in the maintenance of energy balance. Evidence in favor of their hypothesis came from the finding that in man, fasting is associated with lower prostaglandin levels in blood com- pared to post-prandial samples [15]. The studies suggesting a role of insulin in long term regulation in appetite [5,22] would be compatible with the Baile hypothesis as insulin is closely associated with the formation of polyunsaturated fatty acids which are prostaglandin precursors. We have suggested that the hypothalamus acts as a neuroendocrine transducer with the control of food intake involving a delicate balance between a number of neuropep- tides and monoamines [23]. Based on the above information, it seems highly likely that prostaglandins interact with monoamines and peptides responsible for producing the integrated regulation of appetite. In this study we report the effects of PGE2 and PGF2, on a variety of feeding models. The studies reported here allow us to integrate the prosta- glandins into our previously proposed hypothesis of the in- terrelationships of monoaminergic and peptidergic sub- stances involved in the intrahypothalamic regulation of appetite [23,28]. METHOD Male Sprague-Dawley rats (200°250 g) kept under stand- ard lighting conditions (12 hr/day artificial light--0700-1900 hr) and given free access to a standard rat diet and water, were used for all experiments. Cannulas were implanted into the lateral ventricles as previously described [25]. The animals were allowed a minimum of 5 days post-operative recovery before experiments were commenced. Placement of cannula was checked at post mortem by indian ink injec- tion. The food deprivation experiments were conducted using 735