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Performance of alpha7 nicotinic receptor null mutants is impaired in appetitive learning measured in a signaled nose poke task.

Wild-type and mutant mice lacking expression of alpha5, alpha7, beta2, beta3, or beta4 neuronal nicotinic cholinergic receptors (nAChRs) were compared on a signaled nose poke task, a multi-phased task used to measure appetitive learning and impulsivity. In the early phases of training, mutants of all nicotinic lines did not differ compared to wild types in the days to reach criterion when mice were required to nose poke for a sucrose reward on FR1 or FR3 schedules, or in their ability to respond to an auditory clicker to receive a sucrose reward. However, mutants lacking alpha7 nAChRs, but not lines lacking other nAChRs, showed impairments when task difficulty was increased such that an auditory stimulus was presented on a variable schedule and mice were required to withhold their responses until the presentation of the auditory cue to obtain a reward. alpha7 mutants were impaired compared to wild types in appetitive learning as measured by the percentage of conditioned responses but overcame their deficits with extensive training for 10 days. However, when efficiency ratios were used to measure impulsivity, alpha7 mutants exhibited lower efficiency ratios even after 10 days of training. These results support a role of the alpha7 nicotinic receptor in mediating appetitive learning and suggest a potential role for the alpha7 nAChRs in the regulation of behavioral disinhibition.

Analysis of Variance↗

Roles of brain angiotensins II and III in thirst and sodium appetite.

The current study examined the effects of intracerebroventricular (icv) infused aminopeptidase-resistant analogs of angiotensin II (AngII) and angiotensin III (AngIII) on thirst and sodium appetite. The analogs, [D-Asp1D-Arg2]AngII and [D-Arg1]AngIII, were further protected from degradation by pretreatment with the aminopeptidase A inhibitor, EC33, or the aminopeptidase N inhibitor, PC18. Prior to icv infusions, rats were sodium depleted with furosemide, followed by the angiotensin-converting enzyme inhibitor captopril, to block endogenous angiotensin formation. Both angiotensin analogs, at either of the two doses, were capable of eliciting fluid intakes of water and 0.3 M NaCl. Water and saline intakes were increased to a similar extent by 125 and 1250 pmol of [D-Asp1D-Arg2]AngII. [D-Arg1]AngIII produced a dose-dependent increase in water intake, whereas saline intake was equivalently increased by the 125 and 1250 pmol infusions. Pretreatment with EC33 or PC18 decreased water and saline intakes in response to [D-Asp1D-Arg2]AngII, while pretreatment with PC18 altered the time course of the [D-Arg1]AngIII-induced water and saline intakes. The ability of both inhibitors to decrease, but not completely block, AngII analog-induced intakes, coupled with the altered time course of the responses induced by the AngIII analog in the presence of PC18, supports the hypothesis that both AngII and AngIII are active ligands in brain angiotensin-mediated thirst and sodium appetite. However, these results do not resolve the primary question of whether conversion of AngII to AngIII is a prerequisite to dipsogenic and salt appetite responses in the brain.

Angiotensin II↗

A novel method for induction of salt appetite in rats.

A number of procedures exist for the experimental induction of sodium appetite. With the exception of a low sodium diet, nearly all of these methods are invasive, requiring injections, surgery, or both. In addition to stimulating intake of concentrated salt, some of them produce substantial side-effects like reduced food intake and weight gain. The present experiment was designed to evaluate the efficacy of a novel non-invasive method to induce a salt appetite. We investigated the effects of ingesting 100 microM amiloride, a diuretic and natriuretic compound, on urine quantity, electrolyte balance, 0.5 1M sodium chloride (NaCl) intake, water intake, and Na(+)-free chow intake, and weight gain in rats. A water ingestion only group served as control. Consumption of amiloride in mixture with water produced greater loss of urinary Na(+) and intake of 0.51 M NaCl compared with controls. This treatment was without effect on food intake and only modestly influenced weight gain. These results demonstrate a rapid and non-invasive method for the induction of salt appetite free of unwanted side-effects.

Amiloride↗

Light-induced activation of distinct modulatory neurons triggers appetitive or aversive learning in Drosophila larvae.

During classical conditioning, a positive or negative value is assigned to a previously neutral stimulus, thereby changing its significance for behavior. If an odor is associated with a negative stimulus, it can become repulsive. Conversely, an odor associated with a reward can become attractive. By using Drosophila larvae as a model system with minimal brain complexity, we address the question of which neurons attribute these values to odor stimuli. In insects, dopaminergic neurons are required for aversive learning, whereas octopaminergic neurons are necessary and sufficient for appetitive learning. However, it remains unclear whether two independent neuronal populations are sufficient to mediate such antagonistic values. We report the use of transgenically expressed channelrhodopsin-2, a light-activated cation channel, as a tool for optophysiological stimulation of genetically defined neuronal populations in Drosophila larvae. We demonstrate that distinct neuronal populations can be activated simply by illuminating the animals with blue light. Light-induced activation of dopaminergic neurons paired with an odor stimulus induces aversive memory formation, whereas activation of octopaminergic/tyraminergic neurons induces appetitive memory formation. These findings demonstrate that antagonistic modulatory subsystems are sufficient to substitute for aversive and appetitive reinforcement during classical conditioning.

Animals↗

Dipsogenic stimulation in ibotenic DRN-lesioned rats induces concomitant sodium appetite.

The main purpose of this study was to investigate whether dipsogenic stimuli influences the sodium appetite of rats with ibotenic acid lesion of the dorsal raphe nucleus (IBO-DRN). Compared to control, rats microinjected with phosphate buffer (PB-DRN), the ingestion of 0.3M NaCl was enhanced in IBO-DRN at 21 and 35 days after DRN lesion under a protocol of fluids and food deprivation. Despite of similar dipsogenic response observed both in IBO-DRN and PB-DRN treated with isoproterenol (ISO, 300 microg/kg, sc), the 0.3M NaCl intake was again significantly enhanced in IBO-DRN at 21 and 35 days post-lesion. Finally, treatment with polyethylene glycol (PEG, MW=20,000, 20%, w/v, 16.7 ml/kg, sc) induced higher dipsogenic response in IBO-DRN than PB-DRN at 21 day after lesion. In addition, IBO-DRN also expressed higher sodium appetite than PB-DRN, concomitantly with a drinking response. These results suggest that ibotenic lesion of DRN promote an increase of the brain angiotensinergic response, possibly settled within the subfornical organ, through paradigms which increase circulating ANG II levels. The current paper supports the hypothesis that the ibotenic lesion of DRN suppresses a serotonergic component implicated on the modulation of the sodium appetite and, therefore, furthering homeostatic restoration of extracellular fluid volume.

Animals↗

NPY and cohorts in regulating appetite, obesity and metabolic syndrome: beneficial effects of gene therapy.

Neuropeptide Y is the most potent physiological appetite transducer known. The NPY network is the conductor of the hypothalamic appetite regulating orchestra in the arcuate nucleus-paraventricular nucleus (ARC-PVN) of the hypothalamus. NPY and cohorts, AgrP, GABA and adrenergic transmitters, initiate appetitive drive directly through Y1, Y5, GABAA and alpha1 receptors, co-expressed in the magnocellular PVN (mPVN) and ARC neurons and by simultaneously repressing anorexigenic melanocortin signaling in the ARC-PVN axis. The circadian and ultradian rhythmicities in NPY secretion imprint the daily circadian and episodic feeding patterns. Although a number of afferent hormonal signals from the periphery can directly modulate NPYergic signaling, the reciprocal circadian and ultradian rhythmicities of anorexigenic leptin from adipocytes and orexigenic ghrelin from stomach, encode a corresponding pattern of NPY discharge for daily meal patterning. Subtle and progressive derangements produced by environmental and genetic factors in this exquisitely intricate temporal relationship between the two opposing humoral signals and the NPY network promote hyperphagia and abnormal rate of weight gain culminating in obesity and attendant metabolic disorders. Newer insights at cellular and molecular levels demonstrate that a breakdown of the integrated circuit due both to high and low abundance of NPY at target sites, underlies hyperphagia and increased adiposity. Consequently, interruption of NPYergic signaling at a single locus with NPY receptor antagonists may not be the most efficacious therapy to suppress hyperphagia and obesity. Central leptin gene therapy in rodents has been shown to subjugate, i.e. bring under homeostatic control, NPYergic signaling and suppress the age-related and dietary obesity for extended periods and thus shows promise as a newer treatment modality to curb the pandemic of obesity and metabolic syndrome.

Animals↗

Effects of peanut oil load on energy expenditure, body composition, lipid profile, and appetite in lean and overweight adults.

OBJECTIVE: We evaluated the effects of peanut oil intake on appetite, energy expenditure, body composition, and lipid profile in lean and overweight adults. METHODS: In a parallel-arm, long-term feeding trial, lean and overweight participants received a daily peanut oil load in a milk shake equivalent to 30% of their resting energy expenditure for 8 wk. Forty-eight adults (24 lean and 24 overweight, 12 male and 12 female in each group) completed the protocol. Anthropometric indices, appetite, dietary intake, energy expenditure, and plasma lipids were monitored. RESULTS: Energy intake increased significantly in the overweight but not in the lean participants. A statistically significant body weight gain (median 2.35 kg) was also observed among the overweight subjects, although this corresponded to only 43% of the theoretical weight gain. Among overweight subjects, high-density lipoprotein cholesterol increased significantly and low-density lipoprotein cholesterol decreased at week 4, but neither concentration was significantly different from baseline at week 8. Similar, but less marked, changes were observed in lean subjects. Resting energy expenditure was 5% greater (P < 0.01) in the overweight group, but no significant difference was observed in the lean subjects. No marked differences of appetite were observed over time in either group or between overweight and lean participants. CONCLUSION: These data indicate that ingestion of peanut oil elicits a weaker compensatory dietary response among overweight compared with lean individuals. Body weight increased, albeit less than theoretically predicted. The weaker effect of whole nuts on body weight reported in previous studies suggests components other than oil may be responsible.

Adult↗

Salt appetite: a neurohormonal viewpoint.

Sodium is a key component of virtually every mammalian physiological function. As such, many animals have evolved specialized mechanisms for detecting and ameliorating deficits in body sodium, including the development of a robust salt appetite, where normally aversive concentrations of salt are readily consumed during periods of sodium deprivation. Here, we review research spanning more than half a century focusing on the condition and detection of sodium deprivation, the important and unique function of taste in sodium homeostasis, as well as the neurohormonal interactions leading to behaviors aimed at the reversal of sodium deficits. Based on the present literature, we propose a model for the interaction of forebrain and brainstem systems for the mediating circuitry giving rise to salt appetite and discuss the remarkable parallel between what is known about the neurohormonal interactions that regulate salt appetite and those involved in energy homeostasis.

Animals↗

Forebrain circumventricular organs mediate salt appetite induced by intravenous angiotensin II in rats.

Two circumventricular organs, the subfornical organ (SFO) and organum vasculosum laminae terminalis (OVLT), may mediate salt appetite in response to acute intravenous infusions of angiotensin (ANG) II. Fluid intakes and mean arterial pressures were measured in rats with sham lesions or electrolytic lesions of the SFO or OVLT during an intravenous infusion of 30 ng/min ANG II. Beginning 21 h before the 90-min infusion, the rats were depleted of sodium with furosemide and given a total of 300 mg/kg captopril in 75 ml/kg water in three spaced gavages to block the usual salt appetite and to hydrate the rats. No other food or fluids were available for ingestion. Sham-lesioned rats drank 9.3+/-1.2 ml if 0.3 M NaCl alone was available and drank 8.9+/-1.6 ml of saline and 3.7+/-1.6 ml of water if both were available. Either SFO or OVLT lesions reduced the intakes of saline to <5 ml in both conditions and of water to <1 ml. Mean arterial pressure did not differ among the groups and was maintained above 100 mmHg after the depletion and captopril treatments because of the large doses of water. Thus, a full expression of salt appetite in response to an acute intravenous infusion of ANG II requires the integrity of both the SFO and OVLT.

Angiotensin II↗

Effects of (-)-hydroxycitric acid on appetitive variables.

(-)-Hydroxycitric acid (HCA) reportedly promotes weight loss, in part, through suppression of hunger. However, this mechanism has never been evaluated in humans in a controlled study. Eighty-nine mildly overweight females were prescribed 5020-kJ diets for 12 weeks as part of a double-blind, placebo-controlled parallel group study. Forty-two participants ingested 400-mg caplets of Garcinia cambogia 30-60 min prior to meals for a total dose of 2.4 g/day (1.2 g/day HCA). Forty-seven participants ingested matched placebos. Weight and body composition were assessed at baseline and every other week for 12 weeks. Food intake and appetitive variables were assessed at baseline and monthly for 12 weeks. Both groups lost body weight with the active group achieving a significantly greater reduction (3. 7+/-3.1 kg versus 2.4+/-2.9 kg). No effects of the HCA were observed on appetitive variables. The active treatment group did not exhibit better dietary compliance or significant correlations between appetitive variables and energy intake or weight change. This study does not support a satiety effect of HCA.

Adolescent↗

The actual, but not labelled, fat content of a soup preload alters short-term appetite in healthy men.

The effects of the actual and labelled fat content of a soup preload on appetite at a test meal 30 min later were assessed in 16 healthy men. Each participant ate lunch on four occasions, combining two levels of fat energy (Low, 265 kJ or High, 1510 kJ) and two types of label (Low-fat or High-fat), presented as fictitious soup brand names. Preliminary work established that the Low-fat labels produced an expectation of reduced fat content and lower anticipated hedonic ratings, whereas the High-fat labels generated expectations of a high-fat content and above average hedonic ratings. These expectancies were confirmed in the main experiment, with the soups labelled as high fat rated as both more pleasant and creamy than those labelled low-fat, independent of actual fat content. However, intake at the test meal was unaffected by the preload label, but instead reflected the actual fat (hence, energy) content of the soup, with significantly lower food intake after the high-fat soup regardless of the food label. Rated hunger was lower, and fullness higher, at the start of the meal after the high-fat preloads regardless of how they were labelled, while the pattern of appetite change during the test meal was unaffected by preload. These results suggest that realistic food labels can modify the immediate experience of a consumed food, but do not alter appetite 30 min later in healthy men.

Adult↗

Furosemide, sodium appetite, and ingestive behavior.

Sodium appetite is often produced experimentally by using the diuretic furosemide (Furo) to induce a rapid loss of urinary sodium. The present experiments were designed to investigate the dose-dependent relationship between renal and behavioral responses to Furo. We compared the effects of five different Furo doses (0.5, 1, 2, 6, and 10 mg) on 3% NaCl intake, water intake, Na(+)-free chow intake, urine quantity, electrolyte balance, and weight gain in rats. The Na(+) loss produced by Furo injection was dose dependent from 0.5 to 10 mg and did not change across repeated depletions. There was only a weak correspondence, however, between these dose-dependent changes in renal function and subsequent sodium appetite. This suggests that net Na(+) loss is not the only determinant of sodium intake. Moreover, at the two higher doses of Furo, both food intake and weight dropped significantly, but these did not change following the three lower ones. Given these substantial side effects, the preferred dose of Furo for inducing a salt appetite should not exceed 2.0 mg.

Animals↗

Evidence that oral and nutrient reinforcers differentially condition appetitive and consummatory responses to flavors.

Rats tend to increase their intake of a flavor that has previously been paired with either sweet taste or with caloric repletion. However, it is unclear whether such a change in intake is caused by changes in appetitive behaviors such as orienting and approach, or changes in consummatory behaviors and oral responsiveness. Also, it is unclear whether oral reinforcers (sweetness) and postingestive reinforcers (nutrients) lead to the same kinds of behavioral change. In the current experiments, weanling rats with oral and gastric cannulas repeatedly experienced a flavor paired with either sweetness, high caloric density, or neither. Rats were then tested for differences in appetitive olfactory orienting and consummatory oral responsiveness elicited by the flavor. Results suggest that oral reinforcement (sweetness) produces conditioning of appetitive responding to the flavor, while postingestive reinforcement produces conditioning of consummatory responding. A second experiment indicates that these behavioral changes are specific increases in responsiveness conditioned by flavor + unconditioned stimulus (US) pairing, and are unlikely to be nonspecific effects of daily unconditioned stimulus exposure.

Animals↗

Conditioned changes in appetitive and consummatory responses to flavors paired with oral or nutrient reinforcement among adult rats.

Recent studies of the behavioral organization of conditioned flavor preferences have suggested the involvement of at least two separate learning systems-an appetitive response system sensitive to the oral hedonic properties of the reinforcer, and a consummatory response system sensitive to its nutrient properties. However, these prior studies were conducted with weanling rats, that differ from adults in terms of their prior experience with food, their learning competencies, and the peculiar ontogenetic constraints on their behavior. It is, therefore, unknown whether flavor preference behaviors are similarly organized in adult rats. In this experiment, adult rats were trained to associate a specific CS flavor with either the sweet taste or the postingestive nutrient effects of sucrose. Conditioned appetitive orienting and consummatory oral responding to the CS flavors were then measured. Unlike weanling rats, adult rats exhibited both conditioned appetitive behavior and conditioned consummatory behavior in response a CS that was previously paired with either oral hedonic or nutrient reinforcement. These results suggest a set of important developmental changes in the neurobehavioral mechanisms of flavor preference learning in the postweaning period.

Administration, Oral↗

Training in a novel environment improves the appetitive learning performance of the snail, Lymnaea stagnalis.

The effect of novelty, an environmental background variable affecting feeding and appetitive learning performance, was examined in a behavioral study of the pond snail Lymnaea stagnalis. Transfer of snails into a novel aquatic environment (clean water) evoked exploratory behavior which manifested itself in an increased number of spontaneous rasping movements of the mouth over the second to fifth minute after exposure to the novel environment. The intensity of this behavior was much weaker in a familiar environment (used water from the home tank). Similarly, sucrose-induced feeding rates were highest when the snails were given the sucrose stimulus in a novel environment. The effectiveness of appetitive conditioning using tactile stimulus paired with food (Kemenes & Benjamin, 1989a) improved when the snails were subjected to conditioning in a novel environment. Satiety, an internal variable, suppressed the stimulating effects of the novel environment on the spontaneous, unconditioned, and conditioned feeding alike. After training in the novel environment, the conditioned response was retained for up to 12 days and thus provided a robust behavioral paradigm for the extension of the analysis to the neurophysiological mechanisms of factors affecting appetitive learning in molluscs.

Animals↗

Differential influences of corticotropin-releasing factor on memory retention of aversive learning and appetitive learning in rats.

The effects of intraamygdala injections of corticotropin-releasing factor (CRF) on memory retention of aversive and appetitive learnings were examined in the present study. Other than confirming the results of a previous study that a moderate dose of CRF (0.1 microgram) injected into the amygdala facilitated retention performance of an inhibitory avoidance task (electric shock punishment) 24 h after training, we have further found that this effect lasted for a week. However, CRF produced a differential dose-response effect upon memory of an appetitive learning paradigm (sexual reinforcement). CRF at 0.01 microgram enhanced retention at both 24-h and 1-week intervals, while CRF at 0.1 microgram impaired retention in the same task at 1 week only. These results confirm that the amygdala is important in memory processing and suggest that the mechanisms involved in the action of CRF on memory retention of aversive and appetitive learnings are different. The possible differences are also discussed.

Amygdala↗

Differences between appetitive and aversive reinforcement on reorientation in a spatial working memory task.

Tasks using appetitive reinforcers show that following disorientation rats use the shape of an arena to reorient, and cannot distinguish two geometrically similar corners to obtain a reward, despite the presence of a prominent visual cue that provides information to differentiate the two corners. Other studies show that disorientation impairs performance on certain appetitive, but not aversive, tasks. This study evaluated whether rats would make similar geometric errors in a working memory task that used aversive reinforcement. We hypothesized that in a task that used aversive reinforcement rats that were initially disoriented would not reorient by arena shape and thus make similar geometric errors. Tests were performed in a rectangular arena having one polarizing cue. In the appetitive condition water consumption was the reward. The aversive condition was a water maze task with reinforcement provided by escape to a hidden platform. In the aversive condition rats returned to the reinforced corner significantly more often than in the dry condition, and did not favor the diagonally opposite corner. Results show that rats can use cues besides arena shape to reorient in an aversive reinforcement condition. These findings may also reflect different strategies, with an escape/homing strategy in the wet condition and a foraging strategy in the dry condition.

Animals↗

AT(1) receptor blockade with losartan during gestation in Wistar rats leads to an increase in thirst and sodium appetite in their adult female offspring.

We studied the effects of angiotensin II receptor blockade with losartan on thirst and sodium appetite in pregnant Wistar rats and on their adult female offspring. During maternal adaptation to pregnancy, average daily total water intake increased by 63% (P<0.01); NaCl intake by 214% (P<0.001). These changes were not blocked by daily s.c. injections of losartan (50 mg/kg bw i.p.) from gestation day (GD) 2 until GD 19 which implied that maternal AT(1) receptors were not involved in the up regulation of thirst and sodium appetite during pregnancy. Losartan blockade during gestation led to a significant and continued increase in thirst and sodium appetite in the adult female offspring. Daily water intakes were greater in the losartan (LO) group than in the vehicle-injected control group (CO), leading to a total water intake of 1114 +/- 80.6 ml/kg bw compared with 738 +/- 56.7 ml/kg bw (P<0.05) during the 8-day period of observation. Daily sodium intakes were usually 2-3 times greater in the LO group compared with the CO group, amounting to a final cumulative intake of 232 +/- 33 mmol/kg bw compared with 93.8 +/- 16.5 mmol/kg bw (P<0.05) in 8 days. These elevated sodium and water intakes were nearly counterbalanced by the increased renal excretion of water and sodium by fully functional kidneys that were not injured by the drug. Body weights were 10% lower in the LO group at the start but remained unchanged relative to the CO group during the entire 8-day period of observation. Plasma electrolytes, blood hematocrit and carotid MABP in the LO group did not differ from the CO group.

Aging↗