Neuropeptide Y: Behavioral effects in the golden hamster

Neuropeptide Y (NPY) is found abundantly in nervous tissues of vertebrate species including the golden hamster. Centrally-administered NPY has been reported to elicit ingestive behaviors in the rat, squirrel, pig, mouse, and chick. To assess NPY's behavioral effects in a New World rodent that does not increase food intake after deprivation, NPY was injected intracerebroventricularly (10.0-0.04 μg/5 μl) in home-caged golden hamsters with ad lib access to food, water and 5% w/v ethanol solution. Food and fluid intakes, and behavior displays were monitored after NPY injection. NPY promptly increased short-term food intake and observed feeding behaviors at 10.0, 3.3, 1.1, and 0.37 μg NPY, but there was no effect on 24 hr food intake. Water and ethanol intakes were increased only at 10.0 and 0.37 μg NPY, respectively. Resting behaviors decreased at NPY doses that increased feeding, but there were no consistent effects of NPY on any other category of behavior. Results demonstrate that NPY potently stimulates short-term food intake and decreases resting behavior in the golden hamster. The lack of compensatory food intake in deprived hamsters cannot be explained as an insensitivity to the putative orexigenic function of endogenous neuropeptide Y.     

Peripheral ghrelin injections stimulate food intake, foraging, and food hoarding in Siberian hamsters

Fasting triggers many effects, including increases in circulating concentrations of ghrelin, a primarily stomach-derived orexigenic hormone. Exogenous ghrelin treatment stimulates food intake, implicating it in fasting-induced increases in feeding, a consummatory ingestive behavior. In Siberian hamsters, fasting also stimulates appetitive ingestive behaviors such as foraging and food hoarding. Therefore, we tested whether systemic ghrelin injections (3, 30, and 200 mg/kg) would stimulate these appetitive behaviors using a running wheel-based food delivery system coupled with simulated burrow housing. We also measured active ghrelin plasma concentrations after exogenous ghrelin treatment and compared them to those associated with fasting. Hamsters had the following: 1) no running wheel access, free food; 2) running wheel access, free food; or 3) foraging requirement (10 revolutions/pellet), no free food. Ghrelin stimulated foraging at 0-1, 2-4, and 4-24 h postinjection but failed to affect wheel running activity not coupled to food. Ghrelin stimulated food intake initially (200-350%, first 4 h) across all groups; however, in hamsters with a foraging requirement, ghrelin also stimulated food intake 4-24 h postinjection (200-250%). Ghrelin stimulated food hoarding 2-72 h postinjection (100-300%), most markedly 2-4 h postinjection in animals lacking a foraging requirement (635%). Fasting increased plasma active ghrelin concentrations in a time-dependent fashion, with the 3- and 30-mg/kg dose creating concentrations of the peptide comparable to those induced by 24-48 h of fasting. Collectively, these data suggest that exogenous ghrelin, similar to fasting, increases appetitive behaviors (foraging, hoarding) by Siberian hamsters, but dissimilar to fasting in this species, stimulates food intake.     

Relationship between plasma concentrations of immunoreactive beta-endorphin and food intake in rats

Periods of increased food intake in male rats were characterized by significant elevations in the plasma concentrations of immunoreactive beta-endorphin (beta-ep). Administration of 2-deoxy-D-glucose (400 mg/kg) produced rapid and concurrent increases in both food intake and plasma beta-ep. Administration of insulin (10 units/kg) produced large delayed increases in food intake but only modest delayed increases in plasma beta-ep. Spontaneous nocturnal feeding was associated with increased plasma beta-ep. Increases in daytime food intake in rats subjected to 24 hr of food deprivation were also characterized by elevated plasma beta-ep. In all cases examined, those feeding behaviors in male rats which were subject to inhibition by naloxone were characterized by elevated concentration of plasma beta-ep.     

Naloxone reduction of stress-related feeding

The effects of the narcotic antagonist, naloxone, on various types of stress- related feeding in rats were examined. Tail pinch-induced eating of a palatable substance, and 3 hr daytime rat chow intake following acute 2-deoxy-D-glucose (2-DG, 400 mg/kg) administration or 24 hr food deprivation were significantly decreased by low doses (1 mg/kg) of naloxone. Night time food intake was likewise decreased by naloxone (4 mg/kg). In contrast, hyperphagia induced by insulin (10 U/kg) was not decreased by naloxone (0.06–16 mg/kg). These findings suggest that narcotic antagonists should be considered as possible anorexics selective for stress-induced eating, and that endogenous opiates may prove to be another significant factor involved in the control of food intake.     

Food hoarding is increased by food deprivation and decreased by leptin treatment in Syrian hamsters

Compensatory increases in food intake are commonly observed after a period of food deprivation in many species, including laboratory rats and mice. Thus it is interesting that Syrian hamsters fail to increase food intake after a period of food deprivation, despite a fall in plasma leptin concentrations similar to those seen in food-deprived rats and mice. In previous laboratory studies, food-deprived Syrian hamsters increased the amount of food hoarded. We hypothesized that leptin treatment during food deprivation would attenuate food-deprivation-induced increases in hoarding. Baseline levels of hoarding were bimodally distributed, with no hamsters showing intermediate levels of hoarding. Both high (HH) and low hoarding (LH) hamsters were included in each experimental group. Fifty-six male hamsters were either food deprived or given ad libitum access to food for 48 h. One-half of each group received intraperitoneal injections of leptin (4 mg/kg) or vehicle every 12 h during the food-deprivation period. Within the HH group, the hoarding score increased significantly in food-deprived but not fed hamsters (P < 0.05). Leptin treatment significantly decreased hoarding in the food-deprived HH hamsters (P < 0.05). The LH hamsters did not increase hoarding regardless of whether they were food deprived or had ad libitum access to food. These results are consistent with the idea that HH hamsters respond to energetic challenges at least in part by changing their hoarding behavior and that leptin might be one factor that mediates this response.     

Effects of the antiestrogens,MER-25 and CI 628, on rat and hamster lordosis

Antiestrogens were used to test the hypothesis that estrogen exerts a “maintenance,” as well as a “priming,” effect on rat and hamster sexual receptivity as it apparently does for guinea pigs. MER-25 (75 or 150 mg/kg) significantly reduced rat LQ when given ?2 hr or 8 hr after EB injection. MER-25 given at 34 hr (2 hr prior to P) failed to diminish rat LQ. With hamsters, MER-25 in large doses (750 mg/kg) given either at ?2 hr or 34 hr reduced lordosis duration to 40% of controls, but this effect was confounded by severe illness among the MER-25 injected animals. Lower doses failed to block behavior, but still produced some toxicity. CI 628 (50 mg/kg) greatly reduced hamster lordosis duration and increased lordosis latency when given 0 hr, but not 34 hr, after EB. The results are consistent with similar previous work on rats and do not support the concept of estrogen “maintenance” in either rats or hamsters.     

Feeding and drinking responses in the golden hamster following treatment with cholecystokinin and angiotensin II

Drinking and feeding behaviours of female golden hamsters were examined following intracerebroventricular injections of angiotensin II or systemic and intracerebroventricular injections of cholecystokinin octapeptide. Injections of angiotensin II into the brain produced a dose-dependent drinking response in water repleted animals. Systemically, a low dose (0.5 microgram/kg body wt) of cholecystokinin was ineffective at reducing food intake of fasted animals during a 1 hr test. Larger peripheral doses (1.0 to 4.0 microgram/kg body wt), however, were effective at decreasing food intake. Injected in the lateral cerebral ventricle, nanogram doses of cholecystokinin decreased food consumption in a dose dependent manner. These results are discussed in relation to how these peptides regulate feeding and drinking behaviours in other species.     

Acute and subchronic influences of tetrahydrocannabinols on water and food intake, body weight, and temperature in rats.

Experiment 1. The acute effects of delta9-THC (1.25, 2.50, 5.00, and 10.00 mg/kg) and delta8-THC (1.25, 2.50, 5.00, and 10.00 mg/kg) was an approximately equipotent, dose related depression of water intake in water-deprived rats. Animals given hashish, inhaled as smoke, showed a depression of water consumption comparable to rats given the highest dose of either of the synthetic THCs. Water intake after chevril smoke was similar to that seen after vehicle injections. Experiment 2. A dose related depression of water-and-food intake, and reduction of body weight with a gradual recovery was found in rats, maintained on a Limited Time of drinking schedule (LT, 2 hr) and subchronically (21 days) treated with delta9-THC (1.25, 2.50, or 5.00 mg/kg). From the 22nd day all animals were given the vehicle only for 10 days. There were no indications of withdrawal effects due to the drug termination. Reinstating the drug after the 10 day drug free period suggested an increased sensitivity to THC as compared to the 21st injection. Experiment 3. In non-deprived rats delta9-THC caused similar effect as in Exp. 2, although to less extent. From both experiments it is concluded that there is an inhibition or even loss of body weight and that food intake seems more severely depressed than water intake. The temperature recordings suggest that the predominant consequence of lower, behaviorally, effective doses of THC on rectal temperature of rats is hyperthermia rather than hypothermia. Initially this effect was most pronounced for the lowest dose (1.25 mg/kg) but with repeated injections the two higher doses (2.50 and 5.00 mg/kg) showed hyperthermia to the same extent as the lowest dose. Hypothermia was seen after a high dose of delta8-THC (20.00 mg/kg) but after 3 daily injections this effect was gone.     

Role of NPY and its receptor subtypes in foraging, food hoarding, and food intake by Siberian hamsters

Fasting has widespread physiological and behavioral effects such as increases in arcuate nucleus neuropeptide Y (NPY) gene expression in rodents, including Siberian hamsters. Fasting also stimulates foraging and food hoarding (appetitive ingestive behaviors) by Siberian hamsters but does relatively little to change food intake (consummatory ingestive behavior). Therefore, we tested the effects of third ventricular NPY Y1 ([Pro(34)]NPY) or Y5 ([D-Trp(34)]NPY) receptor agonists on these ingestive behaviors using a wheel running-based food delivery system coupled with simulated burrow housing. Siberian hamsters had 1) no running wheel access and free food, 2) running wheel access and free food, or 3) foraging requirements (10 or 50 revolutions/pellet). NPY (1.76 nmol) stimulated food intake only during the first 4 h postinjection ( approximately 200-1,000%) and mostly in hamsters with a foraging requirement. The Y1 receptor agonist markedly increased food hoarding (250-1,000%), increased foraging as well as wheel running per se, and had relatively little effect on food intake (<250%). Unlike NPY, the Y5 agonist significantly increased food intake, especially in foraging animals ( approximately 225-800%), marginally increased food hoarding (250-500%), and stimulated foraging and wheel running 4-24 h postinjection, with the distribution of earned pellets favoring eating versus hoarding across time. Across treatments, food hoarding predominated early postinjection, whereas food intake tended to do so later. Collectively, NPY stimulated both appetitive and consummatory ingestive behaviors in Siberian hamsters involving Y1/Y5 receptors, with food hoarding and foraging/wheel running (appetitive) more involved with Y1 receptors and food intake (consummatory) with Y5 receptors.     

Duration of opiate receptor blockade determines tumorigenic response in mice with neuroblastoma: a role for endogenous opioid systems in cancer

The relationship between the pharmacological properties of an opioid antagonist, naltrexone (NTX), and tumor response was studied in mice with transplanted neuroblastoma (NB). Animals receiving 0.1 mg/kg NTX every 6 hr, which blocked morphine-induced analgesia for 24 hr each day, had a 100% tumor incidence, no deviation in time before tumor appearance, and a 17% decrease from control values in total survival time. In contrast, once daily injections of either 0.1 mg/kg NTX or 0.4 mg/kg NTX (the equivalent of 0.1 mg/kg given 4 times daily), which blocked morphine-induced analgesia for less than 10 hr each day, resulted in a tumor incidence of 20% and 60%, respectively, delays in time prior to tumor appearance of 90% and 65%, respectively, and an increased total survival time of 10% and 24%, respectively, for tumor-bearing mice relative to control levels. Inoculation of NB in control animals resulted in 100% tumor appearance within 16 days and a mean survival time of 36 days. These results show that tumorigenic events are dictated by the duration of opiate receptor blockade rather than the dosage of opiate antagonist, and provide compelling evidence that endogenous opioid systems play a crucial role in neuro-oncogenic expression.     

Variability in development of tolerance to repeated injections of low doses of dl-amphetamine in rats

Male albino rats received injections of saline for 5 days before and 5 days after a series of 10 daily injections of dl-amphetamine, 1 or 5 mg/kg, sc. Core temperatures were measured every 30 min for 4 h after each injection and feeding activity (on a CRF operant schedule) every 30 min throughout. After amphetamine at either 0800 or 2000 h, a dose-related hyperthermia, stereotypic behavior, and an initial inhibition of feeding occurred. This anorexia decreased over the 4-h post injection period only in the evening-injected rats receiving 5 mg/kg. Mean body weights of all groups continued to increase during amphetamine administration. Mean 24-h food intake tended to remain below that in the control period and the hyperthermic response did not change significantly in any group. Initially on withdrawal from amphetamine all groups showed 'rebound' feeding. Taken with earlier reports, these results suggest that tolerance development to amphetamine-induced anorexia, hyperthermia, and stereotypic behavior occurs at different rates and is dependent upon frequency, route, dose, time, the amphetamine used, and whether the diet was restricted.     

Fat pad-specific effects of lipectomy on foraging, food hoarding, and food intake

Unlike most species, after food deprivation, Siberian hamsters increase foraging and food hoarding, two appetitive ingestive behaviors, but not food intake, a consummatory ingestive behavior. We previously demonstrated (Wood AD, Bartness TJ, Am J Physiol Regul Integr Comp Physiol 272: R783-R792, 1997) that increases in food hoarding are triggered by directly decreasing body fat levels through partial surgical lipectomy; however, we did not test if lipectomy affected foraging, nor if the magnitude of the lipid deficit affected food hoard size. Therefore, we tested whether varying the size of the lipectomy-induced lipid deficit and/or foraging effort affected foraging, food hoarding, or food intake. This was accomplished by housing adult male Siberian hamsters in a foraging/hoarding system and removing (x) both epididymal white adipose tissue (EWATx) pads, both inguinal white adipose tissue (IWATx) pads, or both EWAT and IWAT pads (EWATx + IWATx) and measuring foraging, food hoarding, and food intake for 12 wk. The lipectomy-induced lipid deficit triggered different patterns of white adipose tissue mass compensation that varied with foraging effort. Foraging for food (10 wheel revolutions to earn a food pellet) abolished the EWATx-induced compensation in IWAT pad mass. The magnitude of the lipid deficit did not engender a proportional change in any of the appetitive or consummatory ingestive behaviors. EWATx caused the greatest increase in food hoarding compared with IWATx or EWATx + IWATx, when animals were required to forage for their food. Collectively, it appears that the magnitude of a lipid deficit does not affect appetitive or consummatory behaviors; rather, when energy (foraging) demands are increased, loss of specific (gonadal) fat pads can preferentially stimulate increases in food hoarding.     

Evidence for the effect of tryptophan on the pattern of food consumption in free feeding and food deprived rats.

The effects of injections of 50 mg/kg L-tryptophan upon meal size, meal frequency, rate of eating and satiety ratios were measured in rats whose feeding behaviour was monitored continuously over 24-h periods. A number of precautions were taken to minimize the effects of novel or stressful experimental procedures, to prevent the contamination of behaviour during periods of data collection and to maximise the detection of subtle effects on behaviour. In freely-feeding rats tryptophan brought about a significant diminution in the 24-h food intake and significantly reduced meal size. When food deprived rats were tested under similar circumstances tryptophan significantly reduced the size of the first large meal taken after the deprivation period and markedly extended the duration of the post-meal interval. The conditions adopted in this study to improve the sensitivity of the behavioural assay for feeding have made possible the detection of certain small but clear effects of tryptophan on food consumption in rats.     

Sex-specific effects of prolactin on food intake by rats

While prolactin (PRL) has been reported to increase food intake by virgin female rats, its effects on food intake by male rats are relatively unexplored. The present studies examined the possibility that PRL has sex-specific effects on food intake by rats. In the first study, intact female and male rats were given subcutaneous injections of saline vehicle or ovine (o) PRL (1.0 mg/kg) twice daily at 08:00 and 20:00 h for 10 days. Food intake, body weight, and water intake were measured daily. Results indicate that oPRL administration increased food intake by an average of 4.5 g per day in female subjects, but did not significantly alter body weight or water intake. Male rats treated with oPRL did not significantly alter their food intake, even after an additional five days of treatment. In the second study, a wide range of oPRL doses (vehicle, 0.02, 0.2, 2.0, and 20.0 mg/kg/day) were tested in gonadectomized female and male rats. The results indicate that female rats responded to increasingly larger doses of oPRL with greater increases in food intake, with a maximum increase of approximately 6. 1 g per day at a dose of 20.0 mg/kg. In contrast, male rats maintained baseline levels of intake across all oPRL doses tested. These data suggest that PRL has sex-specific effects on food intake.     

Cholecystokinin, behavioral tolerance and tumor-induced anorexia

Cholecystokinin octapeptide (CCK-8, 5 micrograms/kg, IP) was injected daily, for two 4-day periods, into rats bearing the Walker 256 carcinosarcoma (TB) and non-tumor bearing (NTB) control animals. All animals were on a 20 hr food and water deprivation schedule and monitored for food and water intake and bodyweight for 4 hr daily. Food intake was significantly reduced by the daily administration of CCK. Behavioral tolerance to CCK was not observed in either the NTB or TB rats. These results indicate that the parameters describing the phenomenon of behavioral tolerance to CCK are yet to be clearly defined and that peptides other than CCK may underlie the mechanism primarily responsible for producing anorexia associated with cancer.     

The analgesia produced by food deprivation in 4-month old, 14-month old, and 24-month old rats

The analgesia produced by 24 hr of food deprivation was examined in 4-mo, 14-mo, and 24-mo old rats. To assess opioid and hormonal involvement in food deprivation induced analgesia, different groups of rats from each age group were injected with naltrexone (7 mg/kg), dexamethasone (0.4 mg/kg), or equivolume saline. Results revealed that food deprivation produced an equivalent analgesic response in each saline-treated age group. Also, naltrexone and dexamethasone were equally potent in blocking food deprivation induced analgesia in each age group. These results demonstrated that food deprivation activates an endogenous opioid-mediated analgesic system that involves hormonal factors and that this system does not change in function with increasing age.     

The selective serotonin reuptake inhibitor paroxetine does not alter consummatory concentration-dependent licking of prototypical taste stimuli by rats

Serotonin and the 5HT(1A) receptor are expressed in a subset of taste receptor cells, and the 5HT(3) receptor is expressed on afferent fibers innervating taste buds. Exogenous administration of the selective serotonin reuptake inhibitor, paroxetine, has been shown to increase taste sensitivity to stimuli described by humans as sweet and bitter. Serotonergic agonists also decrease food and fluid intake, and it is possible that modulations of serotonin may alter taste-based hedonic responsiveness; alternatively, or in combination, serotonin may interact with physiological state to impact ingestive behavior. In this study, the unconditioned licking of prototypical taste stimuli by rats in brief-access taste tests was assessed following paroxetine administration (0.3-10 mg/kg intraperitoneal). We also measured sucrose licking by rats in different deprivation states after paroxetine (5 mg/kg). In neither experiment did we find any evidence of an effect of paroxetine on licking relative to water to any of the taste stimuli in the brief-access test at doses that decreased food intake. However, in some conditions, paroxetine decreased trials initiated to tastants. Therefore, a systemic increase in serotonin via paroxetine administration can decrease appetitive behavior in brief-access tests but is insufficient to alter taste-guided consummatory behavior.     

Naloxone suppresses intake of highly preferred saccharin solutions in food deprived and sated rats

In repeated tests naloxone (1 mg/kg, sc) suppressed intake of a narrow range of highly preferred saccharin concentrations (0.1 and 1.0%) in nondeprived male rats but a wider range of concentrations (.001-1.0%) following 10 hr. food deprivation. In sated rats a low dose of morphine (0.1 mg/kg, sc) had no effect on intake of low concentrations of saccharin but significantly facilitated intake of the highest (10%) and least preferred concentration. These data support the hypothesis that endogenous opioids can modulate the affective quality of gustatory stimuli.     

Suppression of appetitive behavior in the rat by naloxone: lack of effect of prior morphine dependence

Naloxone (0.3–10 mg/kg) produced a dose-related suppression of eating and drinking in rats that had been deprived of food for 48 hr or water for 24 hr. The suppression of water intake by naloxone was unaltered in rats that had been physically dependent upon morphine one week earlier and which were tolerant to the analgesic effect of morphine at the time naloxone was tested. These results confirm the ability of naloxone to suppress appetitive behavior in the rat but do not resolve the issue of whether or not this effect of naloxone is the consequence of an interaction with an endogenous opioid system.     

Behavioral dependence on phencyclidine in rats

The abuse of PCP continues to be an important medical problem in many urban areas. The probability that dependence on PCP may contribute to its compulsive use and relapse is supported by animal studies demonstrating its dependence liability. In the present study, five rats were housed in operant chambers and trained to respond on a lever under a fixed-ratio 30 schedule of food presentation. They obtained all their daily food during four 30-min response periods occurring every 6 hr. After stable baselines of behavior were established the rats were injected with PCP (3.0-7.5 mg/kg/injection), i.p., 1 hr before each response session for 7-10 days. Following chronic dosing, the drug injections were replaced with saline injections for 10 days. Disruptions in behavior were observed upon cessation of relatively brief chronic exposure to PCP (as little as 7 days) and at relatively low doses (5.6 mg/kg/6 hr = 22.4 mg/kg/day). The behavioral disruption was not accompanied by overt signs of abstinence and persisted for up to 48 hr.