Delta(9)-THC stimulates food intake in Lewis rats: effects on chow, high-fat and sweet high-fat diets

Free-feeding adult male Lewis rats were administered intraperitoneal (i.p.) Delta(9)-tetrahydrocannabinol (THC) in doses of 0.5, 1.0 and 2.5 mg/kg, and effects on food intake were measured at 1, 2, 4, 6 and 24 h postinjection. Rats were fed rat chow, a high-fat diet (HF) or a high-fat sweetened (HFS) diet. Small increases in HF and HFS intake following doses of 0.5 or 1.0 mg/kg were seen at 1, 2 and 4 h, but not 6 or 24 h compared to vehicle intake. Increases following 0.5 and 1.0 mg/kg did not differ from each other at any time point and 2.5 mg/kg produced smaller differences at all time points. There was no difference between HF or HFS intake at any time point although larger increases were seen in the HF group compared to both chow and HFS following 0.5 and 1.0 mg/kg. This work confirms previous data in both humans and rats indicating a stimulatory role for cannabinoids in ingestive behavior.     

8-Hydroxy-2-(di-n-propylamino)-tetralin inhibits food intake in fasted rats by an action at 5-HT1A receptors

The effects of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) on food intake were investigated in food-deprived rats. 8-OH-DPAT (25-100 microg/kg) administered subcutaneously immediately prior to the presentation of food produced a dose-related decrease in food intake in rats that had been fasted for 22 h. The hypophagic effect of 8-OH-DPAT (50 microg/kg) was abolished by pretreatment with the selective 5-HT1A receptor antagonist n-[2-(4-2-methoxyphenyl)-1-piperazinyl]-n-(2-pyridyl) cyclohexanecarboxamide (WAY 10063; 0.3 mg/kg). The results of this study show that the acute dose-dependent depressant effect of 8-OH-DPAT on food intake in fasted rats is mediated by an action at 5-HT1A receptors.     

Eating high fat chow increases the sensitivity of rats to 8-OH-DPAT-induced lower lip retraction

Eating high fat food can alter sensitivity to drugs acting on dopamine systems; this study examined whether eating high fat food alters sensitivity to a drug acting on serotonin (5-HT) systems. Sensitivity to (+)-8-hydroxy-2-(dipropylamino) tetralin hydrobromide (8-OH-DPAT; 5-HT1A receptor agonist)-induced lower lip retraction was examined in separate groups (n=8-9) of rats with free access to standard (5.7% fat) or high fat (34.3% fat) chow; sensitivity to quinpirole (dopamine D3/D2 receptor agonist)-induced yawning was also examined. Rats eating high fat chow gained more body weight than rats eating standard chow and, after 6 weeks of eating high fat chow, they were more sensitive to 8-OH-DPAT (0.01-0.1 mg/kg)-induced lower lip retraction and quinpirole (0.0032-0.32 mg/kg)-induced yawning. These changes were not reversed when rats that previously ate high fat chow were switched to eating standard chow and sensitivity to 8-OH-DPAT and quinpirole increased when rats that previously ate standard chow ate high fat chow. These data extend previous results showing changes in sensitivity to drugs acting on dopamine systems in animals eating high fat chow to a drug acting at 5-HT1A receptors and they provide support for the notion that eating certain foods impacts sensitivity to drugs acting on monoamine systems.     

Opioid-dependent anticipatory negative contrast and binge-like eating in rats with limited access to highly preferred food.

Binge eating and an increased role for palatability in determining food intake are abnormal adaptations in feeding behavior linked to eating disorders and body weight dysregulation. The present study tested the hypothesis that rats with limited access to highly preferred food would develop analogous opioid-dependent learned adaptations in feeding behavior, with associated changes in metabolism and anxiety-like behavior. For this purpose, adolescent female Wistar rats were daily food deprived (2 h) and then offered 10-min access to a feeder containing chow followed sequentially by 10-min access to a different feeder containing either chow (chow/chow; n=7) or a highly preferred, but macronutrient-comparable, sucrose-rich diet (chow/preferred; n=8). Chow/preferred-fed rats developed binge-like hyperphagia of preferred diet from the second feeder and anticipatory chow hypophagia from the first feeder with a time course suggesting associative learning. The feeding adaptations were dissociable in onset, across individuals, and in their dose-response to the opioid-receptor antagonist nalmefene, suggesting that they represent distinct palatability-motivated processes. Chow/preferred-fed rats showed increased anxiety-like behavior in relation to their propensity to binge as well as increased feed efficiency, body weight, and visceral adiposity. Chow/preferred-fed rats also had increased circulating leptin levels and decreased growth hormone and 'active' ghrelin levels. Thus, the short-term control of food intake in rats with restricted access to highly preferred foods comes to rely more on hedonic, rather than nutritional, properties of food, through associative learning mechanisms. Such rats show changes in ingestive, metabolic, endocrine, and anxiety-related measures, which resemble features of binge eating disorders or obesity.     

Absence of clonidine-induced food intake in hamsters

Previous studies support an interaction between noradrenergic and opiate systems in the control of food intake. For example, in both rats and rabbits, food intake stimulated by the noradrenergic agent clonidine is reduced by opiate antagonists. The purpose of the present study was to determine whether or not clonidine stimulated the food intake of non-food-deprived hamsters, a species which appears to lack an opiate-sensitive feeding system. Hamsters fed a chow diet did not increase their food intake when injected with clonidine in doses ranging from 0.05 to 0.25 mg/kg. Furthermore, the animals did not increase their intake of sunflower seeds, a preferred diet for hamsters.     

Sedation and need-free salt intake in rats treated with clonidine

The effect of intraperitoneal injection of clonidine (9-72 microg/kg) on need-free 1.5% NaCl intake and on performance (defined as percent of a complete trial) in the rotarod test, was studied in normovolemic adult male rats. Clonidine (18 and 36 microg/kg) inhibited the 1.5% NaCl intake in a 2-h test at doses that did not alter the performance in the rotarod test. The dose of 36 microg/kg did not inhibit 10% sucrose intake. Only the highest dose (72 microg/kg) of clonidine inhibited the 1.5% NaCl intake and the performance in the rotarod test, and produced signs of sedation. Sedation was determined either by change in posture (immobility or lack of postural tonus) of the animals during the ingestive test or by their performance in the rotarod test. The results suggest that sedation is not a determinant effect on the inhibition of 1.5% NaCl intake induced by clonidine.     

Role of 5-HT1A receptors in the control of food intake in obese Zucker rats of different ages

The present study describes the role of 5-HT1A receptors in the serotonergic control of food intake in obese Zucker rats of different ages. In addition, serotonin (5-HT) and cholecystokinin (CCK) content and 5-HT turnover were determined in various brain regions. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 100 microg/kg) stimulated food intake in 3-month-old lean control rats but inhibited feeding in obese Zucker rats (300 microg/kg). This pattern remained the same in 6-month-old rats. At 10 months of age, 8-OH-DPAT lost its inhibitory activity in the obese rats but still stimulated feeding in lean controls (300 microg/kg). 5-HT levels were higher in the hypothalamus and in the frontal and parietal cortices of 3-month-old obese Zucker rats and were associated with a lower cortical turnover. In the parietal cortex and the hypothalamus of 6-month-old rats, 5-HT levels were still higher, linked with a lower hypothalamic turnover. No differences were observed in 10-month-old rats. CCK content was not different between obese Zucker rats and lean rats. The persistently different feeding responses to 8-OH-DPAT in obese Zucker rats and lean controls may be related to changes in brain 5-HT metabolism in the obese Zucker rats.     

8-OH-DPAT elicits feeding and not chewing: evidence from liquid diet studies and a diet choice test

There have been recent claims that the 5-HT_1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) elicits chewing and eating of solid but not liquid foods. Therefore, the effects of 8-OH-DPAT and another 5-HT_1A agonist gepirone on the consumption of a liquid chow diet, by free feeding male rats, were examined. Both drugs produced a dose-dependent increase in the consumption of liquid diet during a 2 h test. The doses of 8-OH-DPAT and gepirone which increased liquid diet intake in this study were in the same range as those which were found previously to increase food pellet consumption by free feeding rats. The effects of 8-OH-DPAT were also examined in a feeding choice test in which free feeding animals were allowed to choose between food pellets and a liquid chow diet. In this test, 8-OH-DPAT significantly increased total food intake (liquid plus pellet) but had no significant effect on the consumption of either liquid or pellet diets when analysed separately. Thus, there were large individual differences in diet choice after 8-OH-DPAT injection. However, rats did not consistently choose to eat food pellets rather than the liquid diet, as would be predicted if the drug elicited chewing rather than eating. These results provide strong evidence that 8-OH-DPAT elicits a behaviourally specific hyperphagia and not chewing or gnawing.     

Influence of taste and food texture on the feeding responses induced by 8-OH-DPAT and gepirone

Previously it has been shown that 5-hydroxytryptamine (5-HT)_1A agonists such as 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and gepirone increase food intake in free-feeding rats. These experiments were conducted to examine the possible influence of taste and textural factors on the feeding responses induced by these two drugs. Separate groups of non-water-deprived rats were given access to one of a variety of different solutions of saccharin (0.02, 0.04, 0.20 and 2.0% w/v) or water for 2 h each day. Rats were then treated with different doses of 8-OH-DPAT (10, 60 or 100 µg/kg) or gepirone (1 or 2.5 mg/kg) in a repeated measures design. Under saline injection an inverted-U shaped concentration-response curve was obtained, with the highest level of intake occurring in rats drinking from the 0.20% saccharin solution. The highest doses of 8-OH-DPAT and gepirone suppressed drinking of saccharin, particularly over the first 30 min of the test period, leading to a flattening of the concentration response curve. At 2 h post-injection 60 µg/kg 8-OH-DPAT enhanced the consumption of the 0.04% saccharin solution only. In a second experiment, 8-OH-DPAT or gepirone was administered to rats eating either standard pelleted chow or the same food presented in powdered form. Both drugs stimulated feeding. However, interactions with food type were found. At 60 and 100 µg/kg 8-OH-DPAT increased eating of both food types equally, but with 500 µg/kg rats are significantly more of the pelleted food. Gepirone at 1 and 2.5 mg/kg also significantly increased pelleted food intake compared to powdered food intake. These results suggest that taste factors alone are unlikely to be a major determinant of 8-OH-DPAT's effects on food intake. On the other hand, food texture may play a significant role in the capacity to elicit feeding after high doses of both 8-OH-DPAT and gepirone.     

Chronic administration of the antiretroviral nevirapine increases body weight, food, and water intake in albino Wistar rats

Abstract Background: Nevirapine (NVP) is an antiretroviral medication that prevents human immunodeficiency virus (HIV) cells from multiplying in the blood. This study was undertaken to investigate the effect of chronic administration of NVP on body weight, food, and water intake using apparently healthy albino Wistar rats. Methods: Twenty adult albino Wistar rats (50-125 g body weight) were used for the study. Rats in the control group (n=10) were fed normal rodent chow, whereas the NVP group (n=10) were fed by gavage NVP (0.4 mg/kg body weight) two times daily (07.00 h and 18.00 h) in addition to normal rodent chow for 12 weeks. All animals were allowed free access to clean drinking water. Results: Results showed that the mean daily food and water intake in the NVP group were significantly higher (p<0.001) when compared with the control group, respectively. The mean change in body weight in the NVP group was significantly higher (p<0.001) than the control group. Conclusions: These results suggest that chronic administration of NVP may increase body weight in rats, probably due to its stimulatory effects on food and water intake.     

The dopamine D3/D2 receptor agonist 7-OH-DPAT induces cognitive impairment in the marmoset.

Previous work has shown that dopaminergic systems are involved in cognitive function in the common marmoset. The present study investigated the role of dopamine D3 receptors in cognitive performance in the marmoset. The effects of the putative dopamine D3 receptor agonist, 7-OH-DPAT, on performance of a same-day reversal visual object discrimination task were assessed using a miniature Wisconsin General Test Apparatus (WGTA). Within the same test session marmosets acquired a two-choice object discrimination initial task and a reversal task to criterion. 7-OH-DPAT (6-10 microg/kg) significantly impaired reversal task performance only, without affecting acquisition of the initial task. A higher dose of 25 microg/kg 7-OH-DPAT impaired initial task acquisition as well as reversal task acquisition, possibly as a consequence of a nonspecific influence on motor function. The dopamine D2 receptor antagonist (-)sulpiride (5-10 microg/kg) and the alpha2-receptor antagonist yohimbine (50 microg/kg) failed to attenuate the effects of 7-OH-DPAT (6 microg/kg) in this task. In contrast, the dopamine D2/D3 receptor antagonist raclopride (50 microg/kg) significantly attenuated the 7-OH-DPAT-induced impairment of reversal task performance. These results suggest that activation of dopamine D3 receptors produces a selective impairment of aspects of cognitive function in the marmoset.     

Inhibition of Opioid Transmission at the ��-Opioid Receptor Prevents Both Food Seeking and Binge-Like Eating

Endogenous opioids, and in particular μ-opioid receptors, have been linked to hedonic and rewarding mechanisms engaged during palatable food intake. The aim of this study was to investigate the effects of GSK1521498, a novel μ-opioid receptor antagonist, on food-seeking behavior and on binge-like eating of a highly preferred chocolate diet. Food seeking was measured in rats trained to respond for chocolate under a second-order schedule of reinforcement, in which prolonged periods of food-seeking behavior were maintained by contingent presentation of a reward-associated conditioned reinforcer. After reaching a stable baseline in both procedures, animals were treated with GSK1521498 (0.1, 1, and 3 mg/kg; IP) or naltrexone (NTX, 0.1, 1, and 3 mg/kg; SC). The binge eating model was characterized by four temporally contiguous phases: 1-h chow access, 2-h food deprivation, 10-min chow access, and 10-min access to either chocolate-flavoured food or standard chow. During training the rats developed binge-like hyperphagia of palatable food and anticipatory chow hypophagia (anticipatory negative contrast). Both compounds reduced binge-like palatable food hyperphagia. However, GSK1521498 reduced the impact of high hedonic value on ingestion more specifically than NTX, abolishing anticipatory chow hypophagia. GSK1521498 also dose-dependently reduced food seeking both before and after food ingestion, whereas NTX reduced food seeking only after food ingestion. Thus, while both drugs affected the hedonic value of the preferred food, GSK1521498 also directly decreased incentive motivation for chocolate. Selective μ-opioid receptor antagonism by GSK1521498 may have utility as a treatment for reducing maladaptive, palatability-driven eating behavior by reducing the motivational properties of stimuli that elicit the binge eating commonly associated with obesity.     

Delta9-THC induced hyperphagia and tolerance assessment: interactions between the CB1 receptor agonist delta9-THC and the CB1 receptor antagonist SR-141716 (rimonabant) in rats

This study examined effects of the CB1 receptor antagonist/inverse agonist SR-141716 and the CB1 receptor agonist delta9-tetrahydrocannabinol (delta9-THC) on feeding behavior in male Sprague-Dawley rats. Rats were housed individually with free access to regular pelletized laboratory chow [after a 2 weeks handling phase, animals had access to regular chow for 21 h (Study 1) or 22 h (Study 2); high-fat powder food for 3 h in Study 1 and 2 h in Study 2, respectively], and free access to water. Animals were maintained on a reversed 12-h light/dark cycle (dark beginning at noon). Rats were habituated to this type of feeding and light/dark schedule for 3 weeks until a stable baseline for food intake was achieved. In Study 1, animals were examined after administration of delta9-THC alone (dose range 0.1-1.8 mg/kg), SR-141716 alone (dose range 0.03-0.3 mg/kg), and the two drugs combined; injections were given i.p. at the beginning of the second hour after presenting the high-fat diet and drugs were given twice weekly. There was a dose-related increase in high-fat diet intake, peaking at 0.56-1 mg/kg delta9-THC. SR-141716 alone suppressed the high-fat diet intake below control levels. A combination of 0.3 mg/kg SR-141716 and 0.56 mg/kg delta9-THC counteracted the effects on consumption of either drug alone. In Study 2, experimental rats were treated initially with 0.56 mg/kg delta9-THC for six consecutive days; controls received vehicle. Attenuation of the hyperphagia (high-fat diet) was evident after the second injection. Increasing doses of delta9-THC (1 and 1.8 mg/kg, for two and three consecutive days, respectively) did not reinstate the initial hyperphagia. In conclusion, low-to-moderate doses of delta9-THC produced hyperphagia (to a high-fat food source), which was antagonized by SR-141716. SR-141716 singly suppressed intake of the high-fat diet. Delta9-THC-induced hyperphagia dissipated rapidly upon chronic treatment; however, it is unclear whether this reflects pharmacological tolerance or the emergence of a conditioned taste aversion in Study 2.     

A role for serotonin in lipopolysaccharide-induced anorexia in rats

Rats consistently reduce their food intake following injection of bacterial lipopolysaccharides (LPS). Because LPS increases CNS serotonin (5-HT) turnover, and because increases in CNS 5-HT turnover are associated with a decrease in food intake, we conducted a series of studies to examine 5-HT's potential role in LPS-induced anorexia. Chronic CNS 5-HT depletion by cisterna magna (CM) administration of 5,7-dihydroxytryptamine (5,7-DHT) failed to attenuate LPS-induced (100 microg/kg, ip) anorexia. In subsequent experiments, LPS was injected at lights out (hour 0) and [8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT)] or N-CBZ-[(8beta)-1,6-dimethylergolin-8-yl]methylamine (metergoline) was injected at hour 5 - the time when LPS-treated rats become anorectic. Food intake was measured during the subsequent 2 h. In LPS-treated rats, 8-OH-DPAT (62.5, 125, or 250 microg/kg, sc) injection increased food intake. In a 2 x 2 factorial arrangement of LPS and 8-OH-DPAT, 125 microg/kg 8-OH-DPAT increased food intake significantly more in LPS-treated rats than in non-LPS-treated rats (significant LPS x 8-OH-DPAT interaction). In LPS-treated rats, 1 and 5 mg/kg metergoline significantly enhanced food intake. However, in a 2 x 2 arrangement of LPS and metergoline, 1 mg/kg metergoline failed to increase food intake in LPS and non-LPS-treated rats in two separate trials. The ability of the 5-HT(1A) receptor agonist 8-OH-DPAT to attenuate LPS-induced anorexia in rats supports a role of 5-HT in LPS-induced anorexia.     

Gradient of dopamine responsiveness to dopamine receptor agonists in subregions of the rat nucleus accumbens

The present study sought to investigate the possibility that the degree of selectivity of dopamine D3/D2 receptor agonists such as quinelorane, 7-hydroxy-2-dipropylaminotetralin (7-OH-DPAT), quinpirole and apomorphine on dopamine D3 over D2 receptor subtypes can be assessed by measuring dopamine transmission in the shell vs. core compartments of the nucleus accumbens by using microdialysis in freely moving rats. Significant reductions in dialysate dopamine levels compared to vehicle-treated animals were observed in the shell of the nucleus accumbens with 3, 10 and 30 microg/kg quinelorane, 100 microg/kg 7-OH DPAT, 25 and 100 microg/kg quinpirole, and 100 microg/kg apomorphine. In the core subregion, significant reductions in dopamine were seen at 10 and 30 microg/kg quinelorane, 25 and 100 microg/kg 7-OH-DPAT, 100 microg/kg quinpirole and 100 microg/kg apomorphine. However, a significant shell/core dichotomy could only be observed in response to the lowest dose of quinelorane (3 microg/kg) with the shell being hyper-responsive compared with the core. The present findings suggest that quinelorane is one of the most selective dopamine D3 receptor agonists based on its ability to target the shell subregion of the nucleus accumbens.     

The effects of 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) on food intake in non-deprived C57BL6 mice

The effects of the 5HT1A agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) were investigated on food intake in non-deprived mice. 8-OH-DPAT (50-200 mg/kg) administered subcutaneously (s.c.) 5 min prior to presentation of food, produced a dose-related increase in cumulative food intake in C57BC6 mice. The hyperphagic effect of 8-OH-DPAT (100 mg/kg, s.c.) was abolished by concurrent treatment with the 5HT1A receptor antagonist N-[2-(4-2-methoxyphenyl)-1-piperazinyl]-N-(2-pyridyl) cyclohexanecarboxamide (WAY100635; 0.3 mg/kg, s.c.). These data show that 8-OH-DPAT produces an increase in food consumption in non-deprived mice by a 5-HT1A receptor-mediated mechanism of action.     

Differential actions of dopamine receptor antagonism in rats upon food intake elicited by either mercaptoacetate or exposure to a palatable high-fat diet.

Selective dopamine receptor antagonists have been shown to reduce food intake of rats under such regulatory challenge conditions as food deprivation and 2-deoxy-D-glucose-induced glucoprivation, and under such palatable conditions as acute exposure to sucrose solutions. Food intake is increased following either pretreatment with the free fatty acid oxidation inhibitor, mercaptoacetate (MA), or acute exposure to a palatable high-fat source. The present study examined whether equimolar doses (50-800 nmol/kg, s.c.) of either the selective D(1) receptor antagonist, SCH23390, or the selective D(2) receptor antagonist, raclopride, would alter food intake elicited by either MA (70 mg/kg, i.p.) or acute exposure to a high-fat diet (67% ground rat chow, 33% vegetable shortening). SCH23390 significantly and dose-dependently reduced MA-induced feeding with the two higher (400 and 800 nmol/kg) doses eliminating this response after the first 2 h and the two lower (50 and 200 nmol/kg) doses preventing the occurrence of significant MA-induced feeding. Raclopride eliminated MA-induced feeding at the highest dose, and produced dose-dependent reductions at lower doses. A different pattern of dopamine antagonist effects emerged for high-fat intake. The identical dose range of SCH23390 failed to alter high-fat intake. In contrast, whereas the highest (800 nmol/kg) dose of raclopride significantly reduced high-fat intake after 1 h, the middle (200 and 400 nmol/kg) doses of raclopride significantly increased high-fat intake after 2 h. These data are discussed in terms of the modulatory actions of dopamine upon food intake, of the differential actions of dopamine receptor subtypes upon intake under challenge and palatable conditions, and of the potential participation of presynaptic and postsynaptic receptor populations in these responses.     

Effects of d- and l-amphetamine on food intake: evidence for a dopaminergic substrate

The present experiment examined the effects of d- and l-amphetamine on the intake of sugar, sweetened rat chow and unsweetened rat chow in free feeding rats. Rats were injected IP with 4 doses of d- or l-amphetamine (0.0, 0.125, 0.50 and 2.00 mg/kg). Regardless of drug condition, animals were found to prefer sugar over sweetened or unsweetened chow. d-Amphetamine significantly increased food intake at 0.125 and 0.50 mg/kg doses but not at 2.00 mg/kg. l-Amphetamine had no significant effects at any dose. Further, d-amphetamine significantly increased sugar intake but not sweetened or unsweetened chow. Since d- and l-amphetamine are equipotent at releasing noradrenaline, while d-amphetamine is 2 to 5 times more potent at releasing dopamine, the results suggest that d-amphetamine-induced feeding is associated with activation of a dopaminergic substrate.     

Role for dopamine-3 receptor in the hyperphagia of an unanticipated high-fat meal in rats

Behavioral studies have indicated that midbrain dopamine projections arising in the ventral tegmental area and substantia nigra play a central role in integrating violations of expectancy in reward-related paradigms. The present study was designed to assess violations of dietary expectation and the role the dopamine-3 receptor plays in integrating reward-related food intake in violations of expectancy. Two groups of rats were conditioned to a meal-feeding schedule (3 h of access to food per day) in which they received either standard rodent chow or a preferable, high-fat diet. Animals either received the diet they had access to during the training period (no contrast) or the opposite diet (negative and positive contrast). As predicted, animals in the positive contrast condition were hyperphagic compared to no contrast animals. Animals in the negative contrast (high fat to chow) condition were hypophagic compared to no contrast animals. A dopamine agonist specific to the dopamine three receptor, ((+/-)-7-Hydroxy-dipropylaminotetralin HBr) and the dopamine-2 receptor antagonist raclopride were administered in equimolar doses peripherally to assess the involvement of the dopamine receptor subtypes in the violation of expectancy food intake effects. 7-Hydroxy-dipropylaminotetralin HBr blocked the hyperphagia associated with positive contrast and did not disrupt intake in the negative contrast or no contrast paradigm. Raclopride was ineffective at disrupting food intake. These results support the hypothesis that the dopamine-3 receptor is involved in the hyperphagia of an unexpected high fat meal.     

Effects of liraglutide and sibutramine on food intake,palatability, body weight and glucose tolerance in the gubra DIO-rats

Aim:

To validate the gubra DIO-rats as a useful animal model of human obesity.

Methods:

The gubra diet-induced obesity (DIO) rat model was based on male Sprague-Dawley rats with ad libitum access to regular chow and a palatable diet rich in fat and sugar. To evaluate the versatility of the gubra DIO-rats as a valid model of human obesity syndrome, the efficacy of 2 weight loss compounds liraglutide and sibutramine with different mechanisms of action were examined in 7-month-old gubra DIO-rats. Liraglutide (200 μg/kg, sc) was administered bi-daily, and sibutramine (5 mg/kg, po) was administered once daily for 23 d.

Results:

Both the compounds effectively reduced the food intake, body weight and total fat mass as measured by nuclear magnetic resonance. Whereas the 5-HT reuptake inhibitor/5-HT receptor agonist sibutramine reduced the intake of both chow and the gubra-diet, the GLP-1 analogue liraglutide predominantly reduced the intake of the highly palatable diet, indicating a shift in food preference. Sibutramine lowered the insulin sensitivity index, primarily via reductions in glucose-stimulated insulin secretion.

Conclusion:

This animal model responds well to 2 weight loss compounds with different mechanisms of action. Moreover, the gubra DIO-rat can be particularly useful for the testing of compounds with potential effects on diet preference.