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Effects of short- and long-term wheel deprivation on running.

The effects of wheel deprivation on running were explored. Eight male rats, well habituated to wheels, were each deprived of wheels for periods of 0, 1, 3, and 10 h during the night (Experiment 1) and 0, 1, 3, and 10 days (Experiment 2). In Experiment 1, as wheel deprivation lengthened, wheel running in the first 24 h of access increased. After 10 days of wheel deprivation subsequent daily running decreased (by 70%), and feeding was suppressed for several days. This temporary decline may be due to detraining and the rats physical inability to run more. Experiment 3 with 12 rats found that the running increase after 3-h wheel deprivation was proportional to the amount of running normally occurring during the deprivation period. Over the short-term, running appears to be regulated like other appetitive behaviors.

Animals↗

Vagotomy as a treatment for morbid obesity.

Based on animal experiments, on the original clinical observations of Dragstedt, and on similarities with appetitive behavior after jejunoileostomy, truncal vagotomy has been attempted as a treatment for morbid obesity in 13 patients with a mean weight of 123 kg. Weight decreases of 20 to 30 kg (range, 2 to 64 kg) have been observed so far. Impaired gastric emptying alone does not seem to account for the decreases. Possibly, improved glucose tolerance with reduction of hyperinsulinemia and other hormonal and/or neural effects are responsible for weight loss and lack of "hunger." The period of observation is short, yet 2 of the 13 patients seem to be failures, of whom one had gastric hyposecretion before operation. It is too early to consider the procedure for general clinical use, which must await further research efforts.

Adult↗

Plant derivatives in the treatment of alcohol dependency.

The present review summarizes the findings of the effects of extracts of purified compounds from several plants on alcohol intake in alcohol-preferring rats. These include St. John's wort (Hypericum perforatum, HPE), kudzu (Pueraria lobata) and ibogaine (Tabernanthe iboga). Alcohol-preferring (P), Marchigian Sardinian (msP), high-alcohol-drinking (HAD), Fawn-Hooded (FH) rats were allowed to drink alcohol or water voluntarily to establish baseline levels. Pure compounds (puerarin, daidzin, daidzein or analogs) isolated from kudzu, extracts from HPE or ibogaine and its analog were given by either intraperitoneal or oral administration. After acute administration, all agents dose-dependently reduced alcohol intake with minimal effects on food intake. Puerarin and HPE were also effective following chronic treatment. Overall, it is clear that pure compounds (daidzin, puerarin), extracts from St. John's wort, ibogaine and an ibogaine analog suppress alcohol intake in animal models of excessive drinking with minimal effects on other appetitive behaviors. Although the true mechanisms of action of these compounds on alcohol intake are not fully understood, with the current information, it appears that these compounds exert their effects by modulating several neuronal systems implicated in drinking behavior. However, their role in the future of pharmacotherapy for alcoholism will depend upon the outcome of carefully conducted clinical trials.

Alcoholism↗

The NMDA receptor partial agonist, 1-aminocyclopropanecarboxylic acid (ACPC), reduces ethanol consumption in the rat.

The present studies assessed the effects of both systemic and intraaccumbens injections of 1-aminocyclopropanecarboxylic acid (ACPC), and NMDA partial agonist, on ethanol consumption in a limited access procedure in Wistar rats. Systemically administered ACPC reduced ethanol consumption in a dose-dependent manner, while a single dose of ACPC administered bilaterally into the nucleus accumbens also reversibly reduced ethanol consumption. Indirect measures of general appetitive behavior showed no effect of ACPC on weight or water intake, which suggests that this effect of ACPC may be specific to ethanol. These data are compatible with the role of NMDA receptors in modulating ethanol consumption and provide the first data showing that ACPC can reduce ethanol consumption. ACPC has neuroprotective effects and does not show the psychotomimetic effects observed with NMDA receptor agents. Thus, ACPC may be helpful in future clinical studies designed to reduce alcohol use.

Alcohol Drinking↗

The evaluation of brain activity in response to taste stimuli--a pilot study and method for central taste activation as assessed by event-related fMRI.

BACKGROUND: Brain pathways contribute to the regulation of appetite behaviors, and advancements in brain imaging offer new opportunities in determining whether disturbances of these pathways play a role in pathological feeding behaviors in humans. We developed a standardized method for the assessment of brain activation in response to taste stimuli. METHODS: Five healthy control women were positioned in a 1.5 T GE magnet resonance (MR) scanner for functional MR imaging (fMRI). They received 1.0 cm3 samples of 1 M glucose solution or artificial saliva (25 mM KCl, 2 mM NaHCO3). Fluid challenges were delivered by a programmable syringe pump (J-Kem Scientific, St. Louis, MO). E-Prime software (Psychology Software Tools Inc., Pittsburgh, PA) coordinated taste stimulation with MR scanning. Data were analyzed using NeuroImaging software (NIS). RESULTS: Healthy women showed increased orbitofrontal cortex activation when glucose was compared to artificial saliva. In addition, mesial and lateral temporal cortical regions contrasted glucose from artificial saliva. CONCLUSIONS: This study demonstrates a design for the systematic study of brain activation after taste stimulation using fMRI and computer controlled stimulus delivery. The results are consistent with previous studies, showing activation in higher order brain centers that are involved in emotional coding of taste experience.

Adult↗

The role of the central nervous system in the psychoneuroendocrine disturbances of anorexia and bulimia nervosa.

It has been well-recognized that starvation in anorexia and bulimia nervosa causes endocrine disturbances. Such disturbances may help understand why many people with eating disorders cannot easily reverse their illness since people with eating disorders often enter a downward spiraling circle with malnutrition sustaining and perpetuating the desire for more weight loss and dieting. Symptoms, such as obsessions and dysphoric mood, and altered appetitive behavior, may be exaggerated by neuropeptide alterations and thus contribute to this downward spiral. While neuropeptide disturbances do not appear to be a permanent feature or cause or anorexia nervosa, these disturbances are strongly entrenched, and are not easily corrected by improved nutrition or short-term weight normalization. This suggests that therapy should be sustained for months after nutritional normalization.

Anorexia Nervosa↗

Galanin modulates the activity of proopiomelanocortin neurons in the isolated mediobasal hypothalamus of the male rat.

It has become apparent that galanin as well as proopiomelanocortin-derived peptides, such as beta-endorphin, play an important role in the hypothalamic circuitry that regulates neuroendocrine functions and appetite behavior. We have recently shown that GalR1 and GalR2 galanin receptor mRNAs are expressed in proopiomelanocortin neurons of the arcuate nucleus, suggesting a direct modulatory action of galanin on the proopiomelanocortin neuronal system. In the present study, we investigated the effect of galanin on beta-endorphin release and proopiomelanocortin mRNA expression from male rat mediobasal hypothalamic fragments incubated ex vivo. Galanin induced a decrease of spontaneous beta-endorphin release within the first 30-60 min of incubation and this effect was blocked by the galanin receptor antagonist galantide. Co-incubation of galanin with FK-506 (tacrolimus), a calcineurin inhibitor, suppressed the inhibitory effect of galanin on beta-endorphin release, suggesting that calcineurin is involved in the galanin-evoked decrease in beta-endorphin release. Measurement of beta-endorphin levels in the tissues at the end of the incubation period (120 min) revealed that galanin caused a two-fold increase of beta-endorphin peptide concentration in the mediobasal hypothalamic tissues. Concurrently, galanin induced an increase in the mean density of silver grains overlying proopiomelanocortin neurons after 60 min of incubation, an effect antagonized by galantide. Finally, reverse transcription-polymerase chain reaction analysis revealed that the mRNAs for the three galanin receptor subtypes (i.e. GalR1, GalR2, and GalR3) were expressed in the incubated mediobasal hypothalamic fragments. Taken as a whole, our results indicate that galanin plays a modulatory role on proopiomelanocortin neurons and this interrelation contributes to the elucidation of the neural circuitry that controls, among others, gonadotropin-releasing hormone function.

Animals↗

The effect of antagonists selective for mu- and delta-opioid receptor subtypes on alcohol consumption in C57BL/6 mice.

Several studies have demonstrated that non-selective opioid receptor antagonists effectively reduce alcohol consumption in both animal models and at the clinical level. However, research examining the contribution of specific opioid receptor subtypes to this effect has yielded conflicting results. Some of these studies have shown that the effect is contingent upon the action of mu receptors while others have suggested that delta receptors are primarily responsible. The data reported here re-examine this question using the alcohol-preferring C57BL/6 mice. The results of this experiment demonstrate that D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH(2) (CTOP), a mu-selective antagonist, and naltrindole, a delta-selective antagonist, are equally effective at reducing alcohol consumption in a limited access model compared to a saline control group. While there was no specific comparison of the effects of these drugs on alternative appetitive behavior, neither of these drugs had effects on measured off-session food or water consumption. The results of this experiment suggest that alcohol consumption is mediated by both mu- and delta-opioid receptor subtypes.

Alcohol Drinking↗

Acoustic startle reflex in schizophrenia patients and their first-degree relatives: evidence of normal emotional modulation.

We investigated emotional disturbances in 36 schizophrenia patients, 48 of their first-degree relatives, and 56 controls to determine if abnormal affective startle modulation could be associated with genetic risk for schizophrenia. Both patients and relatives had a pattern of startle modulation indistinguishable from controls, with potentiated startle amplitude while viewing negative valence slides and attenuation while viewing positive slides. Patients with flat affect did not differ from those without in startle modulation or slide ratings. The patients and their relatives had lower pleasantness ratings of positive slides and the patients had higher pleasantness ratings of the negative slides than controls. The startle paradigm may not be useful for identifying individuals with a genetic liability for schizophrenia. The results suggest that low-level defensive and appetitive behaviors are unaffected in schizophrenia.

Adult↗

Neuroimaging studies in eating disorders.

The understanding of the eating disorders (EDs) anorexia (AN) and bulimia nervosa (BN) has undergone remarkable advancements in the past decade. Most studies that have been done in AN show brain gray and white matter volume loss during the ill state that, at least in part, remit with recovery. Similar patterns occur for brain phospholipids assessed using magnet resonance spectroscopy (MRS). Imaging studies have been used to provide functional information regarding serotonin neuroreceptor dynamics, regional cerebral blood flow, or cerebral glucose metabolism. Such studies have implicated cingulate, frontal, temporal, and parietal regions in AN. Investigators have found that challenges such as food and body image distortions may activate some of these regions, raising the possibility that such studies may shed light on puzzling AN symptoms, such as body image distortions or extremes of appetitive behaviors. Emerging data suggest these disturbances persist after recovery from AN, suggesting the possibility that these are traits that may create a vulnerability to develop an ED. While fewer studies have been done in BN or binge eating disorder, there may be disturbances of serotonin metabolism in similar brain regions. Taken together, these findings give promise for future investigations with the hope of delineating brain pathways that contribute to the etiology of EDs

Anorexia Nervosa↗

Taste reactivity analysis of 6-hydroxydopamine-induced aphagia: implications for arousal and anhedonia hypotheses of dopamine function.

The deficits in feeding and drinking that result from 6-hydroxydopamine (6-OHDA) lesions of the mesostriatal dopamine system are often explained using either sensorimotor arousal or anhedonia hypotheses. Sensorimotor arousal hypotheses posit that dopamine systems facilitate the capacity of sensory stimuli to activate any motor output. The anhedonia hypothesis suggests that dopamine systems amplify the hedonic impact of positive reinforcers. Natural palatability-dependent ingestive and aversive actions, which are emitted by rats to tastes, provide a sensitive test that can discriminate between these hypotheses: A reduction of sensorimotor arousal should diminish the ability of tastes to elicit any actions, whereas anhedonia should shift the balance between positive and aversive actions. To directly compare these two hypotheses, taste reactivity was examined in rats made aphagic by intranigral 6-OHDA injections. The results did not support either of these predictions: Taste reactivity was essentially unchanged. The persistence of normal taste reactivity argues against both an anhedonia and a global sensorimotor arousal interpretation and provides further evidence that the capacity for hedonics can be neurologically dissociated from motivated appetitive behavior. An incentive attribution hypothesis that can account for the results is discussed, along with its implications for a wide range of phenomena associated with dopamine depletion.

Animals↗

Social contacts and production of 50-kHz short ultrasonic calls in adult rats.

The goal of the study was to provide evidence that the production of 50-kHz calls by adult rats is driven by potential or direct social contacts. The calls have been studied during daily visits to a cage by single or paired rats. Repeated exposure of rats to the cage frequently visited by other rats or direct contact between rats significantly increased the number of 50-kHz calls. The increase in production of 50-kHz calls was reduced by 78% after intrapreoptic-anterior hypothalamic injection of MK-801, an N-methyl-D-aspartate-type glutamate receptor antagonist. Calls emitted in all situations had a similar acoustic profile. It was found that 50-kHz calls were produced in anticipation of, and/or during, direct social contacts among adult rats and were predominantly initiated by olfactory stimuli. The calls seem to express an appetitive behavioral state in which the central glutamatergic mechanism is implicated.

Analysis of Variance↗

Anion size does not compromise sodium recognition by rats after acute sodium depletion.

Amiloride-insensitive sodium taste transduction is severely limited by large anions (i.e., gluconate). We found that in a brief-access taste test, sodium-depleted rats exhibited similar levels of increased licking to several sodium salts regardless of anion but did not increase licking to nonsodium salts compared with water. The enhanced licking of sodium salts was abolished in the presence of amiloride. These results suggest that the amiloride-sensitive taste transduction pathway is not only necessary but that it is also sufficient for sodium identification in rats. Sodium-depleted rats tested with amiloride initiated significantly more trials than nondepleted rats; hence, appetitive behavior was mildly potentiated by depletion, even in the absence of a sodium taste cue. Overall, these findings provide compelling support for the primacy of the amiloride-sensitive taste transduction mechanism and its associated neural pathway in the recognition of the sodium cation.

Animals↗

Comparative aspects of lipid metabolism: impact on contemporary research and use of animal models.

The emerging obesity crisis and consequent concerns for corrective measures and appropriate public policy have stimulated research into causes, prevention, remediation, and health consequences of obesity and associated maladies. Such research areas include eating behavior, appetite control, and food intake regulation as well as the regulation of lipid metabolism, cardiovascular function, endocrine function, and dyslipidemia states utilizing various animal models and cell culture systems. Although the liver has a central role in lipid/fatty acid synthesis and glucose is the precursor for de novo fatty acid synthesis in rodents and humans, in many other species, adipose tissues are the primary sites of lipogenesis. In addition, many species utilize acetic acid as a precursor for fatty acid synthesis. This fundamental difference in the site of fatty acid synthesis and the pattern of consequent lipid trafficking influences overall animal lipid metabolism and the role of regulatory hormones and transcription factors. Researchers utilizing various animal species in targeted biomedical research should be aware of these species differences when interpreting their data. In addition, many animal species are used for food production, recreational, and companion purposes. Understanding the lipid metabolism regulatory mechanisms of such species from a comparative perspective is important for the proper nutrition and health of these animals.

Adipocytes↗

Nonassociative and associative modification of head-waving produced by aversive tentacular stimuli in Aplysia.

Head-waving, a spontaneously occurring exploratory and appetitive behavior of the marine mollusc Aplysia, provides an opportunity to examine mechanisms of learning expressed in a nonreflexive behavior. The present study explores nonassociative and associative forms of learned modification of head-waving produced using an aversive stimulus as reinforcement. Experiments on intact, freely behaving animals demonstrate that training with electric shock as an aversive unconditioned stimulus, delivered unilaterally to the anterior tentacles, produces a learned shift in head-waving behavior away from the side on which shock was applied. This behavioral change is a novel learned behavioral response that is influenced by the topographic location of an aversive stimulus. Furthermore, training with application of tentacle shock reinforcement, contingent upon the animal's head position, produces operant conditioning of head-waving. Thus, anterior tentacle shock is effective as an aversive reinforcer for both nonassociative and operant learning expressed in the head-waving behavior of Aplysia.

Animals↗

Cholecystokinin inhibits tail pinch-induced eating in rats.

Peripheral administration of the COOH-terminal octapeptide of cholecystokinin in doses from 1 to 100 micrograms per kilogram of body weight (0.25 to 25.0 micrograms per rat) significantly antagonized tail pinch-induced eating in rats, an animal model for stress-induced human hyperphagia. Centrally administered cholecystokinin was effective only in high doses (3 micrograms into the cerebral ventricle). The finding that the minimal effective dose of cholecystokinin in suppressing stress-induced appetitive behavior is smaller after peripheral than central administration suggests that the peptide is acting on peripheral, as opposed to central nervous system, substrates.

Animals↗

Dopamine D1 or D2 antagonists enhance inhibition of consummatory ingestive behavior by CCK-8.

A dopamine D1 (SKF-38393, 1 mg)- or D2 (LY-171555, 0.1 mg)-receptor agonist inhibited intake of an intraorally infused solution of sucrose by male rats, a test of consummatory ingestive behavior. Treatment with a D1 (SCH-39166, 0.1 mg) or D2 (raclopride, 0.6 mg) antagonist reversed inhibition by the respective agonist but enhanced the inhibitory effect of cholecystokinin octapeptide (CCK-8; 1.8 micrograms). It was not possible to demonstrate specific effects of D1 and D2 agonists on intake of pellets, a test that does not discriminate consummatory ingestive behavior from appetitive ingestive behavior, i.e., behavior used to obtain food. The results demonstrate specific involvement of dopamine D1 and D2 receptors in inhibition of consummatory ingestive behavior.

Animal Feed↗