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DIURNAL VARIATIONS FOR INHIBITION OF EATING BY CHOLECYSTOKININ AND BOMBESIN. F. Scott Kraly, Psychology Department, Colgate University, Hamilton, New York 13346 U.S.A. Inhibition of eating by cholecystokinin and bombesin was examined in male

Sprague-Dawley rats eating after food deprivation under conditions in which they were determined to be equally hungry when tested at the midpoints of the day and night phases of a 12:12 cycle. Cholecystokinin: Octapeptide of cholecystokinin (CCK-8~ .5-160 U/kg i.p., i U = .05 mcg) was less potent at night than during the day for inhibition of eatin~ sweetened milk. Threshold for inhibition during the day was i U/kg; threshold at night was 2.5 U/k~. The calculated IDr^ for inhibition during the day was 33.1 U/kg; IDgo at night was 50.6 U/~. The .5 and I U/kg doses significantly enhanced eatin~ at night. CCK-8 (5-180 U/kg i.p.) was also less potent at night for inhibi- tion of sham feeding GIBCO diet II6EC in rats with open ~astric fistula: Threshold for inhibition during the day was 5 U/kg; threshold at night was 30 U/kg. The ID~o during the day was 15.1 U/kg; ID~n at night was 64.0 U/k~. The i0 U/kg doseJ~ignificantly enhanced sham feedin~Vat night. CCK (20% pure; 5-180 U/kg i.p.) also was less potent at night than during the day for inhibition of sham feeding: ID~n during the day was 14.4 U/kg; ID~n at night was 24.7 U/kg. Bombesin: Synt~tic bombesin (BBS; 2-32 u~/kg i.p~ inhibit- ed eating of sweetened milk both during the day and at night. While BBS inhibited eating in a dose-related manner during the day (calculated ID50 = 43.9 ug/kg) such that a linear regression line accounted for 85% of the variance, BBS failed to produce a dose-related inhibition at night and the regression line accounted for only 16% of the variance. These results describe diurnal variations in the satiating potencies of cholecystokinin and bombesin for rats eating at the midpoints of the day and night phases. Because the diurnal variation in the satiating potency of cholecystokinin is also observed in sham feeding rats, it appears not to depend upon the effect of exogenous cholecystokinin upon gastric emptying of food into the intestine.

A STOMACH HORMONE MEDIATES SATIETY

Henry S. Koopmans Dept. of Psychology, Columbia University, New York, NY 10027, U.S.A.

In order to distinguish between the role of neural and humoral signals in the termination of a meal, four Lewis rats received supernumerary upper gas- trointestinal tract transplants. The stomach, pancreas, duodenum and jejunum were surgically isolated from inbred donor rats and the transplanted aorta and portal vein were connected to the recipient's abdominal aorta and in- ferior vena cava. The terminal jejunal transection was connected end-to- side to the rat's own jejunum. The transplanted tissue had no extrinsic nerves and the recipient's digestive tract was left essentially untouched.

Two weeks after surgery, a gastric tube was placed in the transplanted stomach, which was maintained by daily 8 ml infusions of the rats' liquid diet at the end of each day. The rats were allowed to feed for8hr/day. On randomized days before feeding began, the transplanted stomach was infused at 1.6 ml/min with either 4 or 8 ml of the rat's normal liquid diet or with 8 ml of a balanced salt solution. The rats reduced their spontaneous food intake to compensate for the amount of diet infused (p<.01). The reduction of intake was not simply due to distension of the transplanted stomach or the abdominal cavity because the infusion of 8 ml of physiological salt solution produced a small but nonsignificant 1.6 ml reduction of intake. These results show that neural signals are not necessary for the compensa- tory reduction of food intake and that a humoral signal must be involved.

In a second experiment, a pyloric clamp was placed on the transplanted

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stomach and 5 ml of liquid diet was infused into the clamped or unclamped stomach. While the infusion produced a slightly more than compensatory re- duction of intake, clamping the stomach made no difference. Since clamping would be expected to hold the food in the stomach, the short-term humoral signal must arise in this organ. Since little food is absorbed from the stomach, the signal is probably a stomach hormone.

BEHAVIORAL TESTS DIFFERENTIATE THE PERIPHERAL AND CENTRAL EFFECTS OF BOMBESIN ON FOOD INTAKE IN RATS. J. Gibbs, Cornell University Medical College and E.W. Bourne Laboratory, The New York Hospital, White Plains, NY 10605, USA.

Intraperitoneal injections of tetradecapeptide bombesin (BBS) produced large, dose-related inhibitions of feeding and sham feeding in rats, with threshold doses of 1 to 4 ~g-kg -I. The doses required to inhibit water intake were four

tames those required to inhibit food intake. The feeding~associ~ted b~havior~ of rats receiving BBS by the intraperitoneal route were normally sequenced when measured by a reliable quantitative technique. The structurally related peptides litorin and gastrin-releasing peptide produced similar effects on food intake and behavior. The structurally unrelated peptides substance P, neurotensin, and thyrotropin~releasing hormone produced varying inhibitions of food intake, but also produced abnormal behaviors and/or disruptions of the normal distribution of meal-associated behaviors. Lateral cerebroventricular injections of BBS also produced large, dose-related inhibitions of food intake, with a threshold dose of i00 ng. The dose- response curve for the inhibition of water intake was the same as that for the inhibition of food intake. Behavioral analysis showed that intracerebro- ventricular bombesin elicited a primary increase in grooming which displaced several other behaviors, including feeding. The results demonstrate (i) that peripheral BBS selectively inhibits feeding and elicits a sequence of behaviors which characterizes normal satiety in the rat, and (2) that intracerebroventricular BBS inhibits feeding but that this action is not primary and is not behaviorally specific. These findings sug- gest (i) that peripheral BBS-like peptides may play a role in normal satiety, and (2) that peripheral BBS does not act solely via the cerebrospinal fluid when it elicits satiety. This research was supported by USPHS grant AM 17240 and an Irma T. Hirschl Career Scientist Award.

STRESS AND FEEDING: THE ROLE OF ENDOGENOUS OPIATES AND CORTICOTROPHIN RE- LEASING HORMONE (CRF). JE Morley and AS Levine, Neuroendocrine Research Laboratory, Minneapolis VA Medical Center, Minneapolis, Minnesota, USA. Clinically it is well recognized that stress can lead to either under- or over-eating. Using the mild tail pinch model of stress induced ea£ing in rats we have shown that the increased feeding that occurs under stress is de- pendent on the activation of endogenous opiates. This form of stress induced eating can be decreased by GI signals such as stomach distension and by the GI hormones, bombesin and CCK. Dynorphin, an endogenous opioid peptide that is an agonist for the kappa receptor is a potent inducer of spontaneous feed- ing after central administration whereas morphiceptin, a mu agonist, has no effect on feeding; and delta agonists can partially reuerse the inhibitory effect of GI hormones on feeding. Both the tail pinch and insulin hypogly- cemic models of stress induced eating produce changes in CNS dynorphin levels measured by RIA. Recently a 41-residue corticotrophin-releasing factor (CRF) has been characterized from the hypothalamus. It has been suggested that