Changes in leptin levels during lactation: implications for lactational hyperphagia and anovulation

In these studies we investigated the time course of changes in circulating leptin levels in lactating rats and the dependence of these changes on the energetic cost of lactation and evaluated the contribution of changes in leptin levels to lactational hyperphagia and infertility. In the first experiment, plasma leptin levels were measured on Days 5, 10, 15, 20, and 25 postpartum in freefeeding lactating rats and age-matched virgin females. Retroperitoneal and parametrial fat pads weights were obtained from the same females. In the second experiment the same measures, together with plasma insulin and prolactin levels, were taken on Days 15 and 20 postpartum from galactophore-cut and sham-operated females. In Experiments 3 and 4, the effects of exogenous leptin administration, either subcutaneously (sc) or intracerebroventricularly (icv), on lactational anovulation, maternal food intake, and dam and litter weights were examined. Circulating leptin levels decreased in lactating rats. Leptin levels were highly positively correlated with fat pad weight. Eliminating the energetic costs of lactation by preventing milk delivery induced dramatic increases in plasma leptin and insulin levels and also increased adiposity. Exogenous leptin administration did not affect length of lactational anovulation but reduced food intake, maternal body weight, and litter weight gain when given centrally and maternal body weight when given systemically. Together, these data show that the energetic costs of lactation are associated with a fall in circulating leptin levels but that these do not make a major contribution to the suppression of reproduction in lactating rats; however, they may be permissive to the hyperphagia of lactation.     

Lactational performance, consummatory behavior, and suppression of estrous cyclicity in rats suckling underfed pups

The role of pups' appetite in the regulation of maternal consummatory behavior (food intake of nursing mothers), lactational performance and postpartum diestrus was studied over a period of 45 days postpartum in rats chronically exposed to either underfed or normally fed pups. Experimental rats (n = 10) daily received 5 pups, 4-10-days-old, that had been deprived of food for the preceding 24 h while under the care of nonlactating foster mothers. Control rats (n = 10) received normally fed pups obtained daily from lactating foster mothers. Throughout the experimental period, the daily milk yield (estimated by litter weight gain), the intake of food and water by the mother, as well as the ratio of litter weight gain to mother's intake of food and water were all markedly higher in rats nursing underfed pups than in rats nursing normally fed pups. After a peak in lactation around Day 15 postpartum, experimental rats produced the same amount of milk during extended lactation as they did in the beginning of lactation, while control rats produced only half the amount of milk during extended lactation as they did in early lactation. Regardless of the nutritional state of the suckling pups, maternal body weight increased progressively over the first four weeks of lactation and remained unchanged during the time of extended lactation. The postpartum diestrus and the subsequent diestrous phase in the time of extended lactation were considerably longer in duration in rats that nursed underfed pups. On Day 45 of lactation, prolactin levels were higher and the adrenal glands were larger in experimental rats than in controls.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of leptin administration on lactational infertility in food-restricted rats depend on milk delivery

Leptin administration has been shown to prevent the disruptive effects of acute food deprivation on reproductive function in cycling females and lactating females. We examined the ability of intracerebroventricular leptin administration to ameliorate the effects of food restriction for the first 2 wk postpartum on length of lactational infertility. Leptin administration did not reduce the effects of food restriction on reproductive function at either time period (days 8-15 and 15-22 postpartum) or dose (1 and 10 microg/day) administered. Because of the sharp contrast between these results and the ability of leptin to offset the effects of acute food deprivation in lactating rats, the remaining studies investigated the possible causes of this difference. Both central and peripheral leptin administration eliminated food deprivation-induced prolongation of lactational infertility, suggesting that neither route of administration nor dose was a factor. However, we noticed that, whereas chronically food-restricted females continue to deliver milk to their young, acutely food-deprived females do not. To test the hypothesis that the continued energetic drain of milk production and delivery might prevent the ability of exogenous leptin administration to eliminate the effects of undernutrition, leptin was administered to food-restricted, lactating rats prevented from delivering milk. In this situation intracerebroventricular leptin treatment completely eliminated the effects of food restriction on lactational infertility, suggesting that leptin contributes to the maintenance of reproductive function via two pathways: direct binding in the central nervous system and through increasing the availability of oxidizable metabolic fuels.     

Effects of food restriction on the length of lactational diestrus in rats

The effect of food restriction (60% of an ad lib ration) for the first 14 days postpartum on serum progesterone levels and the duration of lactational diestrus was determined in rat dams nursing litters of eight pups. Food restricted dams showed a longer period of lactational diestrus than ad lib fed dams. Food restriction also caused an increase in progesterone levels that was maintained beyond the period of food restriction itself. Treatment with the dopamine agonist bromocryptine mesylate (0.5 mg/day) either from Day 1 or Day 9 postpartum onward induced early termination of lactational diestrus in both ad lib and food restricted dams but the effect was more rapid in the ad lib fed than in the food restricted females. In both cases, however, the effects of bromocryptine administration on milk delivery showed a similar time course providing indirect evidence that prolactin suppression was equivalent under both diet conditions. These data suggest that food restriction during lactation results in increased progesterone levels that most likely result from increased prolactin release. Further, while prolactin suppression in food restricted dams reduces the duration of lactational diestrus, the latency to do so is somewhat longer than that seen in ad lib fed females, suggesting that some other mechanism may also be operating to suppress ovulation in the food restricted female.     

Interaction of late pregnancy and lactation in rats.

The effect of pregnancy on lactation was studied during the third week of lactational pregnancy in postpartum pregnant rats with a delay in implantation of only 1 day (1d-LP rats). In an experimental design in which the suckling litter was prevented from consuming solid food, lactational performance was estimated by weighing the ten-pup suckling litters on days 16-21 of lactation or by measuring maternal weight loss after a nursing spell on day 21. In 1d-LP rats, food consumption as well as lactational performance was lower than it was in nonpregnant lactating rats (L rats) and pregnant-lactating rats with a normal long delay of implantation of at least 6 days (LP rats). The time spent by the pups sucking at the nipples was not different among the three groups, but the number of milk ejections was diminished in 1d-LP dams. Restriction of daily food supply during days 16 to 21 of lactation diminished lactational performance more strongly in 1d-LP rats than it did in L rats; 1d-LP rats conserved protein stores and mobilized fewer minerals than did L rats. The weight and composition of the litter in vitro were not affected by the food restriction. In pregnant-lactating rats (LP and 1d-LP rats), the number of early resorptions was increased in comparison with pregnant rats, showing that lactation can affect the earlier stages of pregnancy. It was concluded that late pregnancy does not affect nursing behaviour, but suppresses lactation by restricting maternal food intake and mobilization of maternal stores. Measurements in serum indicate a causative role for oestradiol, but not for leptin.     

Maternal Effort is State Dependent: Energetic Limitation or Regulation?

Many small altricial rodents have a postpartum oestrus and are often simultaneously pregnant and lactating. Negative influences of concurrent pregnancy and lactation on both lactational performance and the litter in utero are commonly observed and have been interpreted as resulting from high simultaneous energetic demands of gestation and lactation. We studied these effects in the precocial guinea‐pig (Cavia aperea f. porcellus) that, like many altricial rodents, has a postpartum oestrus, but in which the peaks of energy expenditure on lactation and gestation are widely separated. This life history allowed to investigate whether physiological regulation other than by energetic limitations may be responsible for allocation conflicts arising when lactation and gestation overlap. By comparing simultaneously pregnant and lactating females with lactating non‐pregnant females, we show that females in the former group nurse less and wean earlier than females of the latter group. In a comparison of litter size, litter mass, and pup mortality of females that had not been lactating during pregnancy with females that had been simultaneously pregnant and lactating, we show that the latter do not reduce investment in the following litter. In our study, energetic constraints on ad libitum fed females are unlikely and we therefore suggest that the results must be explained by regulatory constraints on lactational effort. We point out that this explanation has not been excluded for the effects observed in altricial small mammals.     

Leptin extends the anorectic effects of chronic PYY(3-36) administration in ad libitum-fed rats

Acute administration of peptide YY(3-36) [PYY(3-36)] results in a reduction in food intake in several different vertebrates. However, long-term continuous administration of PYY(3-36) causes only a transient reduction in food intake, thus potentially limiting its therapeutic efficacy. We hypothesized that a fall in leptin levels associated with reduced food intake could contribute to the transient anorectic effects of continuous PYY(3-36) infusion and thus that leptin replacement might prolong the anorectic effects of PYY(3-36). Seven-day administration of 100 microg x kg body wt(-1) x day(-1) PYY(3-36) using osmotic minipumps caused a significant reduction in food intake of ad libitum-fed rats, but only for the first 2 days postimplantation. Circulating levels of leptin were reduced 1 day following continuous infusion of PYY(3-36), and combined leptin infusion at a dose of leptin that had no anorectic effects on its own (100 microg x kg body wt(-1) x day(-1)) prolonged the anorectic actions of PYY(3-36) in ad libitum-fed rats for up to 6 days postimplantation and yielded reduced weight gain compared with either peptide alone. The inhibitory effects of 100 microg x kg body wt(-1) x day(-1) PYY(3-36) on food intake were absent in rats refed after a 24-h fast and substantially reduced at a dose of 1,000 microg x kg body wt(-1) x day(-1) PYY(3-36). Leptin replacement was unable to recover the anorectic effects of PYY(3-36) in fasted rats. Our results suggest that an acute fall in leptin levels is not solely responsible for limiting duration of action of chronic PYY(3-36) infusion, yet chronic coadministration of a subanorectic dose of leptin can extend the anorectic effects of PYY(3-36).     

Dynamics of food intake and blood level of hormones regulating appetite in pregnant and lactating mice

Leptin, insulin, corticosterone regulate food intake. Hyperphagia and hormonal rearrangement are typical for pregnancy and lactation. The aim of the study is to correlate food intake with blood levels of these hormones in pregnant and lactating mice. Food intake, body weight, blood glucose, insulin, leptin and corticosterone levels were measured in virgin C57B1/6J micc and on the day 7, 13,17 of pregnancy, and day 1, 7, 14, 30 postpartum. Insulin sensitivity was measured at the day 7, 17 of pregnancy. Food intake and body weight increased towards the second postpartum week and then decreased. Insulin sensitivity decreased towards the end of the pregnancy. Mothers differed from virgin females in hormones and glucose levels only during pregnancy. Leptin level was decreased at the day 7 of gestation, insulin level - during whole gestation. Glucose fell, and leptin and corticosterone increased from the day 7 to 17. Probably, these hormones affect food intake only in pregnant females and do not influence appetite during lactation.     

Effect of continuous infusions of dexfenfluramine on food intake, body weight and brain amines in rats

The present experiments describe the effects of continuous SC infusion, via osmotic minipump, of dexfenfluramine on food intake and body weight of male and female rats. It was found that the food intake of male rats was reduced by infusions of both 3 and 6 mg/kg/day although tolerance developed within 2-4 days at the lower dose. Further, these rats showed tolerance to an acute anorectic test dose of dexfenfluramine. Body weight loss was sustained by both groups. In older (6-8 mo old) female rats, some of which had previously nursed three litters, the anorectic effects of dexfenfluramine (3 and 6 mg/kg/day) were sustained throughout the 6 day infusion, and weight loss was substantial. The effects did not differ between bred and virgin rats of comparable age. The lower dose of dexfenfluramine produced no depletion of brain serotonin (5HT), although 5HIAA was reduced. Both compounds were depleted by the higher dose. The 3 mg/kg/day dose, in select rat populations, may be a close model for the mode of dexfenfluramine administration to humans.     

Effects of neuropeptide Y on food intake and brain biogenic amines in the rainbow trout (Oncorhynchus mykiss)

Neuropeptide Y (NPY) is one of the most potent stimulants of food intake in mammals, but very little is known about NPY actions in fish. The present study investigated the role of NPY in food intake in the rainbow trout (Oncorhynchus mykiss). Food intake was monitored at different times after intracerebroventricular administration of porcine NPY (4 or 8 microg). Both doses significantly increased food intake at 2 and 3 h, and this effect was dose-dependent. However, 50 h after administration of NPY, food intake was significantly lower than in control fish, and cumulative food intake had returned to levels similar to those seen in the control group. The NPY antagonist (D-Tyr27,36, D-Thr32)-NPY (10 microg) inhibited food intake 2 h after icv administration, but did not block the orexigenic effect of NPY when administered jointly with 4 microg NPY. To identify the NPY receptor subtypes involved in the effects of NPY on food intake, we studied the effects of the Y1 receptor agonist (Leu31, Pro34)-NPY (4 microg), the Y2 receptor agonist NPY(3-36) (4 microg), and the highly specific Y5 receptor agonist (cPP(1-7), NPY19-23, Ala31, Aib32, Gln34)-hPP (4 microg). Short-term (2 h) food intake was moderately stimulated by the Y1 agonist, more strongly stimulated by the Y2 agonist, and unaffected by the Y5 agonist. We found that administration of NPY (8 microg icv) had no effect on aminergic systems in several brain regions 2 and 50 h after NPY administration. These results indicate that NPY stimulates feeding in the rainbow trout, and suggest that this effect is cooperatively mediated by Y2- and Y1-like NPY receptors, not by Y5-like receptors.     

Function and lifespan of corpora lutea in ewes treated with exogenous oxytocin

Oxytocin was administered to Dorset and Shropshire ewes in one experiment and to Dorset ewes in a further 4 experiments. In Exp. 1, concentrations of plasma progesterone and lengths of the oestrous cycle in ewes given oxytocin subcutaneously twice a day on Days 0-3, 2-5, 4-7, 6-9, 8-11, 10-13, 12-15 or 14-17 were similar to those of control ewes. In Exp. 2, intraluteal infusions of oxytocin from Day 2 to Day 9 after oestrus had no effect on concentration of progesterone, weight of CL collected on Day 9 or length of the oestrous cycle. In Exp. 3, intraluteal infusions of oxytocin on Days 10-15 after oestrus had no effect on weight of CL collected on Day 15. In Exp. 4, s.c. injections of oxytocin on Days 3-6 after oestrus had no effect on weight of CL collected on Day 9, concentrations of progesterone or length of the oestrous cycle. In Exp. 5, s.c. injections of oxytocin twice a day did not affect the maintenance and outcome of pregnancy in lactating and nonlactating ewes. Exogenous oxytocin, therefore, does not appear to affect luteal function at any stage of the ovine oestrous cycle although oxytocin has been reported by others to alter ovine CL function.     

Pharmacological actions of the peptide hormone amylin in the long-term regulation of food intake, food preference, and body weight

The ability of amylin to reduce acute food intake in rodents is well established. Longer-term administration in rats (up to 24 days) shows a concomitant reduction in body weight, suggesting energy intake plays a significant role in mediating amylin-induced weight loss. The current set of experiments further explores the long-term effects of amylin (4-11 wk) on food preference, energy expenditure, and body weight and composition. Furthermore, we describe the acute effect of amylin on locomotor activity and kaolin consumption to test for possible nonhomeostatic mechanisms that could affect food intake. Four-week subcutaneous amylin infusion of high-fat fed rats (3-300 microg.kg(-1).day(-1)) dose dependently reduced food intake and body weight gain (ED(50) for body weight gain = 16.5 microg.kg(-1).day(-1)). The effect of amylin on body weight gain was durable for up to 11 wks and was associated with a specific loss of fat mass and increased metabolic rate. The body weight of rats withdrawn from amylin (100 microg.kg(-1).day(-1)) after 4 wks of infusion returned to control levels 2 wks after treatment cessation, but did not rebound above control levels. When self-selecting calories from a low- or high-fat diet during 11 wks of infusion, amylin-treated rats (300 microg.kg(-1).day(-1)) consistently chose a larger percentage of calories from the low-fat diet vs. controls. Amylin acutely had no effect on locomotor activity or kaolin consumption at doses that decreased food intake. These results demonstrate pharmacological actions of amylin in long-term body weight regulation in part through appetitive-related mechanisms and possibly via changes in food preference and energy expenditure.     

Influence of neuropeptide Y (NPY) on food intake and growth of penaeid shrimps Marsupenaeus japonicus and Penaeus semisulcatus (Decapoda: Penaeidae)

The effects of neuropeptide Y (NPY) administered intramuscularly or orally on postlarvae (PLs) of two penaeid species were investigated in this study. In experiment 1, food intake (FI) of Marsupenaeus japonicus PLs (0.96 g), injected with NPY at 0.6 microg per g BW, was investigated within 48 h posttreatment. In experiment 2, oral administration of NPY (at doses of 0, 0.125, 0.25, 0.5 microg g(-1) food) on feed intake and growth performance of Penaeus semisulcatus PLs (0.27 g) was examined for 6 weeks. In experiment 1, NPY injection significantly increased average daily FI of M. japonicus PLs within the first 24 h compared to the control (P<0.05), but its stimulatory effect decreased on the second day (P>0.05). The increase in FI was 33% during the first 24 h and 17% during the next 24 h. In experiment 2, significant (P<0.05) differences were found among the groups in terms of weight gain and food utilization (P<0.05). Mean FI significantly increased (as much as 1.3-fold over the control) when NPY was orally administered at doses from 0.125 to 0.5 microg g(-1) feed. There was a positive relationship between FI and final weight (y=-0.972+2.098x, R(2)=0.81) and between FCE and NPY doses in the diets (y=45.37+3.46x, R(2)=0.91). The present findings indicated for the first time that NPY is a potent stimulator of food intake when administered either intramuscularly or orally to penaeid shrimps.     

Alterations in the activities of rat tissue hexose monophosphate dehydrogenases in response to premature weaning and dietary restriction at mid-lactation

Summary The activities of the hexose monophosphate dehydrogenases increased in adipose tissue, remained unchanged in liver and decreased in mammary gland following the weaning of rats at mid-lactation (day 14). When dietary intake was restricted at mid-lactation, the activities of the hexose monophosphate dehydrogenases increased in adipose tissue, decreased in liver, but were unaltered in mammary gland. Premature weaning on day 14 postpartum resulted in maternal increases in both plasma insulin and glucose, which peaked at day 16. The plasma insulin levels decreased from day 14 to day 18 postpartum in the normal lactating rat, and a similar trend was observed for animals on a restricted dietary intake. Daily food consumption in the lactating rat decreased from 50 g to 20 g after premature weaning. The live weight of pups raised on dams given a restricted food intake from day 14 had decreased by day 17 postpartum, whereas an increase in daily live weight gain was recorded for the litters from the lactating controls. The results demonstrate that the activities of the hexose monophosphate dehydrogenases are regulated differentially between tissues of the lactating rat.     

Lactational estrus induction in the Mexican hairless sow

The purpose of this study was to determine the effects on the reproductive performance of the Mexican hairless pig (MHP) while inducing fertile lactational estrus. Lactational estrus was induced on day 8, postpartum, in 20 primiparous sows during two consecutive reproductive cycles. Boar presence and temporary litter withdrawal were used as stimuli. Group I did not receive stimuli (control, C); group II had a 15 min boar stimulus (B); group III had litter withdrawal for 4 h (LW), and group IV received both stimuli (B + LW). Fertile estrus was detected by sow behavior, exfoliative vaginal cytology, and 17 beta-estradiol and progesterone samples. Individual stimuli did not induce fertile lactational estrus; nevertheless, when used together, both stimuli induced 100% of females into estrus, and 80% of them got pregnant while lactating. The partial withdrawal of the litter had a significant and positive effect on the number of live born piglets. Sows pregnant during lactation had shorter reproductive cycles, by not having non-productive days and litter size was greater. Pregnancy induction during lactation allowed the Mexican hairless sow to reduce the period between parturition's without diminishing the lactation length and litter performance.     

Leptin and neuropeptide Y (NPY) modulate nitric oxide synthase: further evidence for a role of nitric oxide in feeding.

Recent studies have suggested a role for nitric oxide in the regulation of food intake. Neuropeptide Y (NPY) is one of the most potent orexigenic agents. Chronic administration of leptin decreases food intake. This study examined the effects of NPY and leptin on nitric oxide synthase (NOS) in the hypothalamus. Previously it has been demonstrated that obese (ob/ob) mice have elevated NOS levels in the hypothalamus. In this study we demonstrated that the administration of leptin (6 microg/day) subcutaneously (SC) for 3 days decreased body weight (P < 0.001) and food intake P < 0.001) in obese (ob/ob) mice as expected. In addition, leptin decreased NOS in the hypothalamus nu 37% (P < 0.01) and in brown adipose tissue by 69% (P < 0.01) but not in white adipose tissue. NPY was administered intracerebroventricularly to CD-1 mice at doses of 0.25 and 0.50 microg. Mice were sacrificed 15 min after injection and NOS was measured in their hypothalami. NPY at the lower dose increased NOS in the hypothalamus by 147%. These results, taken together, with previously published studies support the concept that nitric oxide may play a role as a mediator of the effects of NPY and leptin on food intake. The alterations of NOS in brown adipose tissue following leptin administration could result in changes in blood flow or metabolism in the brown fat.     

Nutrient Specific Feeding and Endocrine Effects of Jejunal Infusions

Intestinal nutrient infusions result in variable decreases in food intake and body weight based on the nutrient type and the specific intestinal infusion site. Only intrajejunal infusions of fatty acids decrease food intake beyond the calories infused. To test whether this extra‐compensatory decrease in food intake is specific to fatty acids, small volume intrajejunal infusions of glucose (Glu) and casein hydrolysate (Cas), as well as linoleic acid (LA) were administered to male Sprague–Dawley rats. Equal kilocalorie (kcal) loads of these nutrients (11.4) or vehicle were infused into the jejunum over 7 h/day for five consecutive days. Food intake was continuously monitored and body weight was measured daily. After the infusion on the final day, rats were killed and plasma collected. Intrajejunal infusions of LA and Glu, but not Cas, suppressed food intake beyond the caloric load of the infusate with no compensatory increase in food intake after the infusion period. Rats receiving LA and Glu infusions also lost significant body weight across the infusion days. Plasma glucagon‐like peptide‐1 (GLP‐1) was increased in both the LA and Glu rats compared with control animals, with no significant change in the Cas‐infused animals. Peptide YY (PYY) levels increased in response to LA and Cas infusions. These results suggest that intrajejunal infusions of LA and Glu may decrease food intake and body weight via alterations in GLP‐1 signaling. Thus, particular nutrients are more effective at producing decreases in food intake, body weight, and inducing changes in peptide levels and could lead to a novel therapy for obesity.     

Differential regulation of apoptosis in the corpus luteum of pregnancy and newly formed corpus luteum after parturition in rats

Apoptosis contributes to luteal regression in many species. In the postpartum rat, there are two different types of corpora lutea (CL) in the ovary: CL of pregnancy (CLP) and newly formed CL (NCL). To investigate the regulation of apoptosis in the two different types of CL during luteal regression, apoptosis and caspase-3 activity were examined in the CL obtained on Days 7, 15, and 21 of pregnancy and Days 0, 1, 3, 5, 7, and 9 postpartum. Furthermore, the effect of lactation on apoptosis in the CL was examined in two groups of postpartum rats: lactating rats that nurse more than 10 pups, and nonlactating rats that nurse no pups. Apoptotic cells were detected after Day 21 of pregnancy. In the CLP, remarkable increases in the number of apoptotic cells on Days 5 and 9 postpartum were observed in nonlactating rats (P < 0.01), but not in lactating rats. Changes in caspase-3 activity in the CLP were not consistent with those in number of apoptotic cells. In the NCL, an increase in apoptosis was found only on Day 5 postpartum in nonlactating rats (P < 0.01), but not in lactating rats. Changes in caspase-3 activity in the NCL were consistent with those in number of apoptotic cells. In conclusion, apoptosis is, at least in part, involved in luteal regression after parturition, and lactation appears to inhibit apoptosis. This study also suggests the presence of a caspase-3-independent mechanism for apoptosis in CLP regression in the rat.     

Effects of hindbrain melanin-concentrating hormone and neuropeptide Y administration on licking for water, saccharin, and sucrose solutions

Melanin-concentrating hormone (MCH) and neuropeptide Y (NPY) are orexigenic peptides found in hypothalamic neurons that project throughout the forebrain and hindbrain. The effects of fourth ventricle (4V) infusions of NPY (5 microg) and MCH (5 microg) on licking for water, 4 mM saccharin, and sucrose (0.1 and 1.0 M) solutions were compared to identify the contributions of each peptide to hindbrain-stimulated feeding. NPY increased mean meal size only for the sucrose solutions, suggesting that caloric feedback or taste quality is pertinent to the orexigenic effect; MCH infusions under identical testing conditions failed to produce increases for any tastant. A second experiment also observed no intake or licking effects after MCH doses up to 15 microg, supporting the conclusion that MCH-induced orexigenic responses require forebrain stimulation. A third experiment compared the 4V NPY results with those obtained after NPY infusions (5 microg) into the third ventricle (3V). In contrast to the effects observed after the 3V NPY injections and previously reported forebrain intracerebroventricular (ICV) NPY infusion studies, 4V NPY failed to increase meal frequency for any taste solution or ingestion rate in the early phases of the sucrose meals. Overall, 4V NPY responses were limited to intrameal behavioral processes, whereas forebrain ICV NPY stimulation elicited both consummatory and appetitive responses. The dissociation between MCH and NPY effects observed for 4V injections is consistent with reports that forebrain ICV injections of MCH and NPY produced nearly dichotomous effects on the pattern of licking microstructure, and, collectively, the results indicate that the two peptides have separate sites of feeding action in the brain.     

Intraventricular insulin potentiates the anorexic effect of corticotropin releasing hormone in rats

Intraventricular corticotropin releasing hormone (CRH) suppresses food intake and body weight as a stress response. Insulin, acting within the brain, also suppresses food intake and body weight, and this suppression is related to caloric homeostasis. We determined if increased insulin within the brain potentiates the anorexic effects of intraventricular CRH. Rats were food deprived for 17 h each day and then given 30-min access to Ensure. One-half received continuous third ventricular infusion of synthetic cerebrospinal fluid via osmotic minipumps, and one-half received insulin (0.6 mU/day). During the infusion, rats also received 0, 0.1, 1.0, or 5.0 microg of CRH into the lateral ventricle just before access to Ensure. Insulin alone had no effect on Ensure intake or body weight. CRH dose dependently reduced Ensure intake in both groups, and the reduction was greater in the insulin group. Hence, central insulin potentiated the ability of centrally administered CRH to suppress food intake. These findings suggest that stress-related influences over food intake, particularly those mediated via CRH, interact with relative adiposity as signaled to the brain by central insulin.