Effects of cholecystokinin octapeptide (CCK-8) on food intake in adult and aged rats under different feeding conditions

The effects of CCK on food intake were investigated under fixed feeding conditions in comparison to a test meal taken after 16 h of food deprivation. The experiments were performed on young adult rats (8 weeks old) as well on aged rats (23 months old). Intraperitoneal CCK-8 (8 and 40 μg/kg) significantly reduced the size of a test meal following 16-h food deprivation. This effect was independent of the age of the rats. However, under fixed feeding conditions neither of the doses used in this study reduced food intake in the young adult rats, whereas the highest dose of 40 μg/kg did so in the aged rats. These results suggest that the hypophagic effect of exogenous CCK-8 depends on experimental conditions, food intake being reduced after a period of food deprivation but not under a fixed feeding regimen in adult animals. Furthermore, the data suggest that age is a factor contributing to the complex behavioral actions of CCK, because only old animals were more susceptible to an anorectic action of CCK under the fixed feeding schedule. An explanation may lie in an interaction of other known behavioral effects of CCK (e.g., anxiogenic, mnemonic action) with its effects under the different feeding schedules.     

The GLP-1 agonist exendin-4 reduces food intake in nonhuman primates through changes in meal size

Exendin-4 (Ex4), a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, has been shown to reduce food intake and suppress gastric emptying in rodents and humans. In this study we investigated the effects of peripheral administration of Ex4 on food intake and meal patterns in adult male rhesus macaques. Rhesus macaques (n = 4) that had been trained to lever press for food pellets were injected intramuscularly 15 min before the start of their 6-h daily feeding period. Ex4 was given at doses of 0.10, 0.32, 0.56, 1.0, and 3.0 microg/kg. Ex4 suppressed food intake in a dose-dependent manner, with the 3.0 microg/kg dose completely preventing feeding during the 6-h period and the 0.10 microg/kg dose suppressing intake by 17%. Doses of 0.32, 0.56, 1.0, and 3.0 microg/kg caused significant reductions in cumulative intake at all six hourly time points. Ex4 inhibited food intake through a specific effect on meal size. Meal size was significantly reduced in a dose-dependent manner with significant reductions at the 0.32 and 1.0 microg/kg doses (P < 0.05). Day 2 and 3 intakes returned to baseline levels with no compensation for Ex4-induced feeding suppression. Administration of doses of 0.32 and 0.56 microg/kg Ex4 over 5 consecutive days led to sustained reductions in intake with no evidence of compensation. Again, these reductions were due to specific effects on meal size. These results demonstrate that activation of GLP-1 pathways has potent effects on the controls of meal size and overall food intake in a nonhuman primate model.     

Suppression of food intake and body weight gain by naloxone in rats

The effect of acute and chronic administration of naloxone on food acquisition and weight gain in rats was studied in 3 experiments. One injection of a sparingly-soluble salt of naloxone in slow-release vehicle markedly lowered mean food intake over that of control rats injected with the vehicle only. Mean body weight of the naloxone-injected rats was significantly lower than that of the control group for one week.Repeated evening injections (2000 h) of naloxone hydrochloride in saline tended to reduce the night-time feeding below control levels throughout the 10-day period of naloxone administration. Food intake was significantly lower in the 4- and 8-h periods after the first injection of naloxone than that on the preceding saline control night. The initial decreases were offset by increased day-time feeding so that total daily food intake was not significantly altered over the 10 days. When saline was substituted for naloxone, food intake increased.Rats given naloxone following 24 h of fasting consumed significantly less food and gained less weight during 4 h of access to food compared to those receiving saline. After a 48-h fast naloxone-treated rats also gained significantly less body weight than those given saline, but the reduction in food intake was not statistically significant. These results suggest the possibility that endorphins may have a modulating effect on feeding activity.     

Salmon calcitonin reduces food intake through changes in meal sizes in male rhesus monkeys

Amylinergic mechanisms are believed to be involved in the control of appetite. This study examined the effects of the amylin agonist, salmon calcitonin, on food intake and meal patterns in adult male rhesus monkeys. Fifteen minutes before the onset of their 6-h daily feeding period, monkeys received intramuscular injections of various doses of salmon calcitonin (0.032, 0.056, 0.1, 0.32, and 1 microg/kg) or saline. Salmon calcitonin dose dependently reduced total daily and hourly food intake, with significant decreases at the 0.1, 0.32, and 1 microg/kg doses. Daily food intake was reduced by approximately 35%, 62%, and 96%, at these doses, respectively. An analysis of meal patterns revealed that size of the first meal was significantly reduced across the dose range of 0.056 to 1 microg/kg, while average meal size was reduced with the 0.32 and 1 microg/kg doses. Meal number was only affected at the 1 microg/kg dose. Repeated 5-day administration of the 0.1 microg/kg dose resulted in a reduction in daily food intake only on injection day 2, while significant reductions in food intake were observed on all five injection days with a 0.32 microg/kg dose. Daily food intake was also reduced for 1 day after the termination of the 5-day injections of the 0.32 microg/kg salmon calcitonin dose. These sustained reductions in intake were expressed through decreases in meal size. These data demonstrate that salmon calcitonin acutely and consistently decreases food intake mainly through reductions in meal sizes in nonhuman primates.     

Urocortin 1 administered into the hypothalamic supraoptic nucleus inhibits food intake in freely fed and food-deprived rats

Peptides of the corticotropin-releasing hormone/Urocortin (CRH/Ucn) family are known to suppress appetite primarily via CRH₂ receptors. In the rat hypothalamic supraoptic nucleus (SON), synthesis of both Ucn1 and CRH₂ receptors has been reported, yet little is known about the effects of Ucn1 in the SON on feeding behaviour. We first established the dose-related effects of Ucn1 injected into the SON on the feeding response in both freely fed and 24-h food-deprived rats. A conditioned taste avoidance paradigm was performed to investigate possible generalised effects of local Ucn1 treatment. Administration of Ucn1 into the SON at doses equal to or higher than 0.5 μg significantly decreased food intake in both freely fed and food-deprived rats. The Ucn1-mediated suppression of food intake was delayed in freely fed as compared to food-deprived animals. Conditioning for taste aversion to saccharine appeared at 0.5 and 1 μg of Ucn1. Both the early and the delayed onset of anorexia observed after intra-SON injection of Ucn1 under fasting and fed conditions, respectively, suggest the possible involvement of different CRH receptor subtypes in the two conditions, while the conditioned taste aversion seems to be responsible for the initial latency to eat the first meal in these animals.     

Evidence for the role of hindbrain orexin-1 receptors in the control of meal size

Hypothalamic orexin neurons project to the hindbrain, and 4th-ventricle intracerebroventricular (4th-icv) injection of orexin-A treatment increases food intake. We assessed the effects of hindbrain orexin-A and the orexin-1-receptor antagonist SB334867 on meal pattern in rats consuming standard chow. When injected 4th-icv shortly before dark onset, lower doses of orexin-A increased food intake over a 2-h period by increasing the size of the first meal relative to vehicle, whereas the highest dose increased food intake by causing the second meal to be taken sooner. Conversely, hindbrain SB334867 reduced food intake by decreasing the size of the first meal of the dark phase. We also examined the effects of 4th-icv orexin-A and SB334867 on locomotor activity. Only the highest dose of orexin-A increased activity, and SB334867 had no effect. In addition, hindbrain SB334867 induced c-Fos in the nucleus of the solitary tract. These data support the suggestion that endogenous hindbrain orexin-A acts to limit satiation. Both orexin-A and the pancreatic satiation hormone amylin require an intact area postrema to affect food intake, so we asked whether 4th-icv orexin-A impairs the satiating effect of peripheral amylin treatment. Amylin reduced the size of the first meal of the dark cycle when rats were pretreated with 4th-icv saline, yet amylin was ineffective after 4th-icv orexin-A pretreatment. Using double-label immunohistochemistry, we determined that some orexin-A fibers in the area postrema are located in proximity to amylin-responsive neurons. Therefore, hindbrain orexin-A may increase food intake, in part, by reducing the ability of rats to respond to amylin during a meal.     

Effect of i.c.v. infusion of the alpha-MSH agonist MTII on meal patterns in male rats following nicotine withdrawal

The present study explored the role of endogenous alpha-MSH in the alteration of meal patterns induced by nicotine (NIC) withdrawal. Male Sprague Dawley rats bearing third ventricle cannulas were placed in computerized food intake monitors. On days 1-21, the rats were given 4 mg/kg/day of NIC or saline (SAL) in four equal i.p. doses during the dark period. NIC suppressed (P < 0.05) food intake only during the first week. The normalization of food intake occurred when the reduced meal size of the NIC injected rats was countered by an increase in meal number. Despite the normalization of 24-h food intake, body weight in NIC rats was decreased (P < 0.05) for 21 days. On day 22, the rats were divided into 4 groups (n's = 7-8 each) and injected into the third ventricle with various doses of the alpha-MSH agonist MTII or artificial cerebrospinal fluid (aCSF): SAL + aCSF, SAL + MTII, NIC + aCSF, NIC + MTII. Infusion of MTII (30 ng/rat) suppressed (P < 0.01) dark phase food intake in both groups, but the NIC + MTII group ate (P < 0.05) more than the SAL + MTII group. Meal number during the dark phase was suppressed by MTII, but the NIC + MTII group took significantly more meals that the SAL + MTII group. Infusion of MTII suppressed meal size in SAL and NIC treated rats, but this effect was attenuated in NIC treated rats. All meal parameters normalized by the day after i.c.v. infusion. These data indicate that NIC treatment differentially affects the neural controls of meal number and meal size and attenuates the suppression by MTII of meal number and meal size.     

Peptide YY(3-36) inhibits gastric emptying and produces acute reductions in food intake in rhesus monkeys

Peptide YY3-36 [PYY(3-36)], a gastrointestinal peptide that is released into the circulation in response to ingesting a meal, has recently been suggested to play a role in controlling food intake. PYY(3-36) has been reported to inhibit food intake following peripheral administration in rodents and in human subjects. To more fully characterize the potential feeding actions of PYY(3-36), we examined the ability of a dose range of PYY(3-36) (0.3-3.0 nmol/kg) to affect liquid gastric emptying and daily 6-h food intake in male rhesus monkeys. Intramuscular PYY(3-36) produced a dose-related inhibition of saline gastric emptying that was maximal at a dose of 3 nmol/kg. Intramuscular PYY(3-36) administered before daily 6-h food access produced significant feeding reductions at doses of 1 and 3 nmol/kg. Analyses of the patterns of food intake across the 6-h period of food access revealed that PYY(3-36) increased the latency to the first meal and reduced average meal size without altering meal number. Although single doses of PYY(3-36) reduced intake, a suppressive effect on food intake was not sustained over multiple administrations across successive days. Together, these data suggest that PYY(3-36) has the ability to reduce food intake in acute test situations in nonhuman primates. Whether this is a physiological action of the endogenous peptide remains to be determined.     

Amylin receptor blockade stimulates food intake in rats

Amylin is postulated to act as a hormonal signal from the pancreas to the brain to inhibit food intake and regulate energy reserves. Amylin potently reduces food intake, body weight, and adiposity when administered systemically or into the brain. Whether selective blockade of endogenous amylin action increases food intake and adiposity remains to be clearly established. In the present study, the amylin receptor antagonist acetyl-[Asn(30), Tyr(32)] sCT-(8-32) (AC187) was used to assess whether action of endogenous amylin is essential for normal satiation to occur. Non-food-deprived rats received a 3- to 4-h intravenous infusion of AC187 (60-2,000 pmol.kg(-1).min(-1)), either alone or coadministered with a 3-h intravenous infusion of amylin (2.5 or 5 pmol.kg(-1).min(-1)) or a 2-h intragastric infusion of an elemental liquid diet (4 kcal/h). Infusions began just before dark onset. Food intake and meal patterns during the first 4 h of the dark period were determined from continuous computer recordings of changes in food bowl weight. Amylin inhibited food intake by approximately 50%, and AC187 attenuated this response by approximately 50%. AC187 dose-dependently stimulated food intake (maximal increases from 76 to 171%), whether administered alone or with an intragastric infusion of liquid diet. Amylin reduced mean meal size and meal frequency, AC187 attenuated these responses, and AC187 administration alone increased mean meal size and meal frequency. These results support the hypothesis that endogenous amylin plays an essential role in reducing meal size and increasing the postmeal interval of satiety.     

The pattern of feeding of first instar nymphs of Schistocerca americana

ABSTRACT The feeding behaviour of nymphs Schistocerca americana (Drury) was recorded throughout the light phases of the first stadium using a behavioural event recording program on a microcomputer. Most food was ingested on day 4 of the stadium, very little on day 1 and none on day 6, the final day of the stadium. Only 26–45% of the total food intake over the stadium occurred during the dark periods and more food was eaten in the last 4 h of each light period than earlier. Feeding occupied only about 5% of the total time. Variation in food intake was a consequence primarily of changes in the numbers of meals. After day 1, the average meal size did not change significantly. Meal length increased relatively slightly compared with meal size as a consequence of an increase in the proportion of time spent feeding in each meal as meal size increased. Meal size was correlated with the length of the previous interfeed suggesting a volumetric regulation. The distribution of pauses within meals was also consistent with the thesis that meal size is governed by the level of excitation in the central nervous system at the start of the meal.     

Ovariectomy-induced changes in food motivation in the rat

Following ovariectomy, adult female rats did not increase their food-reinforced bar pressing during 30-min tests, but they responded significantly more frequently for food than did control animals during 2- and 24-hr bar-press tests. Meal pattern data obtained during the 24-hr test demonstrate that ovariectomy increases meal size and decreases meal frequency, although the reduction in the number of meals did not fully compensate for the alteration in meal size. These findings suggest that ovariectomy does not increase the motivation to initiate a meal, but does result in the taking of a larger meal. The implication of these findings to body-weight set-point interpretations of ovarian obesity are briefly discussed.     

Expression of dopaminergic receptors in the hypothalamus of lean and obese Zucker rats and food intake

As revealed by previous microdialysis studies, basal and food intake-accompanied dopamine release significantly differs in the hypothalamus of obese vs. lean Zucker rats. In the present study, we determined whether dopaminergic receptors are also compromised in obesity. Dopaminergic D(1) and D(2) receptor mRNA expression was studied in the ventromedial hypothalamus (VMH), lateral hypothalamic area (LHA), and the adenohypophysis (AH) of obese and lean Zucker rats using RT-PCR technique. In obese Zucker rats, we found an upregulation of D(1) receptor mRNA in the VMH and AH and a downregulation in the LHA, whereas D(2) receptor mRNA was downregulated in both the VMH and LHA, but not changed in the AH, compared with lean rats. Also, an increase of D(1) receptor staining was seen in the paraventricular nucleus of obese rats by immunohistochemistry. We selected the VMH to test if the observed changes in the dopamine receptor expression of obese rats induce behavioral sensitization to dopamine as expressed by hyperphagia. The overnight food-deprived rats received a single VMH injection (10 nmol) of sulpiride (D(2) receptor antagonist) or saline as control, then food was provided and 1-h food intake was measured. Food intake after sulpiride vs. saline injection was greater in obese rats but was not different in lean rats. Our data suggest that downregulation of D(2) receptor in the hypothalamus at least in the VMH induces behavior sensitization for having large meals. Low D(2) receptor expression may be causal for an exaggerated dopamine release observed in obese rats during food ingestion and for reduced satiety feedback effect of dopamine. High level of D(1) receptor expression in the VMH and low in the LHA may also contribute to the specific feeding pattern in obese rats represented by large meal size and low meal number.     

Failure of tryptophan load-induced increases in brain serotonin to alter food intake in the rat

The effects on food consumption of 50 and 100 mg/kg $\text{1}$-tryptophan injections, versus control saline treatment, were compared in 24-hour food-deprived rats at two time points in the rats' daily light-dark cycle. No effect of the two tryptophan doses, relative to the saline treatment, on food intake was observed, although tryptophan loading significantly raised brain tryptophan, serotonin, and 5-hydroxyindoleacetic acid levels, in a dose-dependent manner, over baseline concentrations. Implications of these data for serotonergic modulation of food intake regulation are considered.     

Food deprivation and the regulation of meal size in larvae of Chrysopa carnea

ABSTRACT. The course of repletion and the effects of food deprivation on meal size were explored in three experiments on larvae of Chrysopa carnea (Neuroptera). Feeding to repletion was found to occur within the first 30 min of exposure to food. Meal size increased as an ogival function of deprivation, up to the limit of gut capacity. Behavioural components involved in the initiation of feeding were little affected by deprivation and did not appear to be inhibited by distention of the gut. Termination of a meal may be mediated by the stimulation of prey-release behaviour, rather than by inhibition of feeding.     

Nesfatin-1(30-59) but not the N- and C-terminal fragments, nesfatin-1(1-29) and nesfatin-1(60-82) injected intracerebroventricularly decreases dark phase food intake by increasing inter-meal intervals in mice

Nesfatin-1 is an 82 amino acid N-terminal fragment of nucleobindin2 that was consistently shown to reduce dark phase food intake upon brain injection in rodents. We recently reported that nesfatin-1(1-82) injected intracerebroventricularly (icv) reduces dark phase feeding in mice. Moreover, intraperitoneal injection of mid-fragment nesfatin-1 (nesfatin-1(30-59)) mimics the food intake-reducing effects of nesfatin-1(1-82), whereas N-terminal (nesfatin-1(1-29)) and C-terminal fragments (nesfatin-1(60-82)) did not. We therefore characterized the structure-activity relationship of nesfatin-1 injected icv to influence the dark phase meal pattern in mice. Mouse nesfatin-1(1-29), nesfatin-1(30-59), nesfatin-1(60-82) or vehicle was injected icv in freely fed C57Bl/6 mice immediately before the dark phase and food intake was monitored using an automated episodic feeding monitoring system. Nesfatin-1(30-59) (0.1, 0.3, 0.9 nmol/mouse) induced a dose-related reduction of 4-h food intake by 28%, 49% and 49% respectively resulting in a 23% decreased cumulative 24-h food intake compared to vehicle at the 0.3 nmol/mouse dose (p<0.05). The peak reduction occurred during the 3rd (-96%) and 4th hour (-91%) post injection and was associated with a reduced meal frequency (0-4h: -47%) and prolonged inter-meal intervals (3.1-times) compared to vehicle (p<0.05), whereas meal size was not altered. In contrast, neither nesfatin-1(1-29) nor nesfatin-1(60-82) reduced dark phase food intake at equimolar doses although nesfatin-1(60-82) prolonged inter-meal intervals (1.7-times, p<0.05). Nesfatin-1(30-59) is the active core of nesfatin-1(1-82) to induce satiety indicated by a reduced meal number during the first 4h post injection. The delayed onset may be indicative of time required to modulate other hypothalamic and medullary networks regulating nocturnal feeding as established for nesfatin-1.     

Patterns of Brain Activation and Meal Reduction Induced by Abdominal Surgery in Mice and Modulation by Rikkunshito

Abdominal surgery inhibits food intake and induces c-Fos expression in the hypothalamic and medullary nuclei in rats. Rikkunshito (RKT), a Kampo medicine improves anorexia. We assessed the alterations in meal microstructure and c-Fos expression in brain nuclei induced by abdominal surgery and the modulation by RKT in mice. RKT or vehicle was gavaged daily for 1 week. On day 8 mice had no access to food for 6–7 h and were treated twice with RKT or vehicle. Abdominal surgery (laparotomy-cecum palpation) was performed 1–2 h before the dark phase. The food intake and meal structures were monitored using an automated monitoring system for mice. Brain sections were processed for c-Fos immunoreactivity (ir) 2-h after abdominal surgery. Abdominal surgery significantly reduced bouts, meal frequency, size and duration, and time spent on meals, and increased inter-meal interval and satiety ratio resulting in 92–86% suppression of food intake at 2–24 h post-surgery compared with control group (no surgery). RKT significantly increased bouts, meal duration and the cumulative 12-h food intake by 11%. Abdominal surgery increased c-Fos in the prelimbic, cingulate and insular cortexes, and autonomic nuclei, such as the bed nucleus of the stria terminalis, central amygdala, hypothalamic supraoptic (SON), paraventricular and arcuate nuclei, Edinger-Westphal nucleus (E-W), lateral periaqueduct gray (PAG), lateral parabrachial nucleus, locus coeruleus, ventrolateral medulla and nucleus tractus solitarius (NTS). RKT induced a small increase in c-Fos-ir neurons in the SON and E-W of control mice, and in mice with surgery there was an increase in the lateral PAG and a decrease in the NTS. These findings indicate that abdominal surgery inhibits food intake by increasing both satiation (meal duration) and satiety (meal interval) and activates brain circuits involved in pain, feeding behavior and stress that may underlie the alterations of meal pattern and food intake inhibition. RKT improves food consumption post-surgically that may involve modulation of pain pathway.     

Influence of the subfornical organ on meal-associated drinking in rats

A lesion of the subfornical organ (SFO) may disrupt drinking after a meal of dry chow as it does drinking after intragastric administration of hypertonic saline. Food and water intakes of SFO-lesioned (SFOX) and sham-lesioned rats were measured during 90-min tests following various lengths of food deprivation. During the tests, all rats began eating before they began drinking. After 20-24 h of food deprivation, latency to begin drinking after eating had started was longer for SFOX than for sham-lesioned rats. Plasma osmolality was elevated by 2-3% in both lesion groups at 12 min, the latency for sham-lesioned rats to drink, but SFOX rats nevertheless continued eating and delayed drinking. Eating after shorter 4-h food deprivations and ad libitum feeding produced more variable drinking latencies and less consistent effects of SFO lesion. During 24 h of water deprivation, SFO lesion had no effect on the suppression of food intake and did not affect food or water intakes during the first 2 h of subsequent rehydration. These findings indicate that the SFO is involved in initiating water intake during eating and in determining drinking patterns and the amount of water ingested during a meal.     

Behaviour of worker subcastes in the fire ant, Solenopsis invicta, in response to proteinaceous food

ABSTRACT. The effects of division of labour on response behaviour to food in the red imported fire ant, Solenopsis invicta Buren, were examined to determine if caste members differ in amount of food taken, in rate of food transfer, or in internal distribution of food; and to see if food availability, time, or temporal subcaste pairing affect feeding behaviour. To measure differences in behaviour we fed radioiodinated albumin mixed with egg yolk to colonies containing larvae, queens, and (a) foragers and nurses, or (b) foragers and reserves, or (c) nurses and reserves. Samples were taken over a 72-h period and radioactivity in the head, thorax and abdomen of each worker was determined. There were significant differences between nurses, foragers and reserves in quantity of food consumed, rate of transfer, and internal distribution of radioactivity. These differences were related to their respective roles of foraging, food storage and transfer, and brood tending. The quantity of food taken per subcaste was dependent on the total amount of food in the colony, with transfer rates differing between subcastes as the quantity of food in the colony increased. The rate at which protein was transferred between subcastes was slower in the reserves than that in either foragers or nurses. Therefore, reserves may serve as a temporary store of protein for the colony.     

Circadian rhythms of food intake in gastroduodenally-ulcerated rats: effects of three anti-ulcer drugs

The effects of three anti-ulcers drugs on the temporal distribution of food intake and of the two parameters, meal size and meal frequency, were studied in ulcerated and non-ulcerated rats exposed to light-dark (LD 12:12) cycles. Experimental ulceration with indomethacin reduces the amplitude of meal frequency and brings the acrophase forward, compared with non-ulcerated animals. These effects were reversed by the oral administration of either ranitidine, sucralfate or pirenzepine along with the food. However, the administration of either pirenzepine or sucralfate alone to non-ulcerated rats is accompanied by significant (P less than 0.05) changes in the circadian patterns of meal size and meal frequency without the total daily food intake being affected in any way (pirenzepine treatment caused large intake of food during the light period while sucralfate treatment resulted in marked food intake during the dark period). The results indicate that circadian modification of meal patterns in the ulcerated rats are attributable to indomethacin-induced gastrointestinal mucosal injury and anti-ulcer medications.     

Interaction of apolipoprotein AIV with cholecystokinin on the control of food intake

Apolipoprotein AIV (apo AIV) and cholecystokinin (CCK) are peptides that act both peripherally and centrally to reduce food intake by decreasing meal size. The present study examined the effects of intraperitoneally administered bolus doses of recombinant apo AIV, CCK-8, and a combination of subthreshold doses of apo AIV and CCK on 4-h food intake in rats that were fasted overnight. Apo AIV at 100 microg/kg reduced food intake significantly relative to the saline control for 1 h, as did doses of CCK-8 at or above 0.125 microg/kg. Doses of apo AIV (50 microg/kg) or CCK (0.06 microg/kg) alone had no effect on food intake. However, when these subthreshold doses of apo AIV and CCK were administered together, the combination produced a significant inhibition of food intake relative to saline controls (P < 0.001), and the duration of the effect was longer than that caused by the administration of either apo AIV or CCK alone. The satiation effect produced by CCK-8 + apo AIV was attenuated by lorglumide, a CCK1 receptor antagonist. We conclude that, whereas the intraperitoneal administration of doses of either recombinant apo AIV or CCK at or above threshold levels reduces food intake, the coadministration of subthreshold doses of the two peptides is highly satiating and works via CCK1 receptor.