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Alteration and recovery of appetitive behaviour following nerve section in the starfish Asterias rubens.

The starfish Asterias rubens is an invertebrate deuterostome whose nervous system shows remarkable regenerative properties. To understand when full functionality of a damaged part of the nervous system recovers, and to follow nerve regeneration in detail, we carried out behavioural experiments with 29 starfishes that had the nerve in one of the arms sectioned in a mid-arm position. Loss and recovery of normal behaviour was followed by video analysis of animal performance in an appetitive behavioural test. When compared to 13 control (unoperated) animals, the appetitive response of freshly sectioned animals is normal initially, progressively deteriorates up to 40 days after the lesion, and then gradually improves until 60 days, when recovery is complete. This is true only when one of the leading arms in the appetitive test is a sectioned arm; turning the starfish so that both the leading arms facing the prey are unlesioned, results in normal behaviour even at 40 days after the cut. Thus, regeneration is a multi-step process whose time course coincides with anatomical regeneration. At intermediate times the animals have coordination problems in an appetitive behaviour test and these give some insights into how arms may inter-communicate to organize concerted movements.

Animals↗

In utero development of fetal thirst and appetite: potential for programming.

Thirst and appetite-mediated ingestive behavior develop and are likely programmed in utero, thus preparing for newborn and adult ingestive behavior. Fetal swallowing activity is markedly different from that of the adult, as spontaneous fetal swallowing occurs at a markedly (six-fold) higher rate compared with spontaneous adult drinking activity. This high rate of fetal swallowing is critical for the regulation of amniotic fluid volume and the development of the fetal gastrointestinal tract. Disordered fetal swallowing has been associated with both a decrease (oligohydramnios) and increase (polyhydramnios) in amniotic fluid volume. Both conditions are associated with a significant increase in perinatal morbidity and mortality, and limited treatment modalities are currently available. The mechanisms underlying the high rate of human fetal swallowing are regulated, in part, by tonic activity of central angiotensin II, glutamate N-methyl-D-aspartate receptors, and neuronal nitric oxide synthase. Fetal hypertonicity-mediated dipsogenesis is likely programmed in utero, as offspring of water-restricted ewes demonstrate a programmed syndrome of plasma hypertonicity, with significant hematologic and cardiovascular alterations. Similar to dipsogenic mechanisms, peripheral and central fetal orexic mechanisms also develop in utero, as demonstrated by increased fetal swallowing after both oral sucrose infusion and central injection of neuropeptide Y. The role of leptin in regulating fetal ingestive behavior is interesting because, contrary to actions in adults, leptin does not suppress fetal ingestive behavior. Teleologically, this may be of value during the newborn period, as unopposed appetite stimulatory mechanisms may facilitate rapid fetal and newborn weight gain. An adverse intrauterine environment, with altered fetal orexic factors during the critical developmental period of fetal life, may alter the normal setpoints of appetitive behavior and potentially lead to programming of adulthood hyperphagia and obesity. Further research is needed to delineate the mechanistic relationship between the intrauterine environment and the development of the setpoints of adult appetite and thirst.

Animals↗

Sodium preference and appetite in rats in an operant protocol.

An operant task that may simulate natural foraging was used to study in Sprague-Dawley rats the need-free choice between water and various concentrations of NaCl solution, and the induction of sodium appetite during chronic deoxycorticosterone acetate (DOCA) treatment. The task imposed a fixed ratio foraging or procurement cost for access to each fluid. The relative preference for NaCl over water when both had the same procurement cost was similar to the preference/aversion function that has been reported for this strain of rat under free drinking conditions. As the procurement cost increased, the number of bouts taken per day of both water and NaCl decreased and the mean bout size increased. Administration of DOCA produced an increase in NaCl intake under all conditions, and this appetite was manifest as discrete episodes whose frequency and size were inversely related. Natural observations of sodium appetite in mammals, such as excursions to, often remote, mineral deposits, imply an episodic organization of this behavior. This report is the first laboratory simulation of environmental factors that affect the episodic or temporal organization of sodium appetite.

Animals↗

Environmental enrichment reduces impulsivity during appetitive conditioning.

Although environmental enrichment is presumed to enhance learning, appetitive behavior may also be altered by this experience: anticipatory responding for sucrose is reduced in environmentally enriched (EE) rats [van der Harst, J.E., Baars, A.M. and Spruijt, B.M. Standard housed rats are more sensitive to rewards than enriched housed rats as reflected by their anticipatory behaviour. Behav Brain Res 2003;142:151-156]. To assess the impact of differential environmental experience on learning and appetitive behavior, we trained 17 EE and socially isolated (SI) rats in a three-phase, operant-shaping procedure for sucrose reinforcement. In phase one, a feeder cue was paired with sucrose availability. In phase two, a nose poke to either one of two lit holes on the opposing wall activated the feeder cue. In phase three, the feeder cue was elicited by a poke to a single lit hole. While acquisition rates in phase one and phase two were similar, EE animals reached phase-three criteria [completion of 100 trials in 45 min and 15 or fewer bad pokes] faster than SI animals. These two groups showed similar session completion rates, reinforced and non-reinforced licking responses, and overall behavioral activity during phase three acquisition; however, SI rats performed more bad pokes (responses to the non-lit hole after nose-poke cue onset) and intertrial interval (ITI) pokes during this training period. Because all ITI (and presumably many bad) pokes were initiated before onset of nose-poke cue, this difference indicates greater anticipatory responding in SI animals. This experience-dependent alteration in appetitive behavior may explain, in part, the tendency of SI rats to show attenuated learning rates in appetitive contexts in which complex contingencies exist.

Animals↗

The corticotropin-releasing factor system as a mediator of the appetite-suppressing effects of stress in fish.

A characteristic feature of the behavioural response to intensely acute or chronic stressors is a reduction in appetite. In fish, as in other vertebrates, the corticotropin-releasing factor (CRF) system plays a key role in coordinating the neuroendocrine, autonomic, and behavioural responses to stress. The following review documents the evidence implicating the CRF system as a mediator of the appetite-suppressing effects of stress in fish. Central injections of CRF or the related peptide, urotensin I (UI), or pharmacological treatments or stressors that result in an increase in forebrain CRF and UI gene expression, can elicit dose-dependent reductions in food intake that are at least partially reversed by pre-treatment with a CRF receptor antagonist. In addition, the appetite suppressing effects of various environmental, pathological, physical, and social stressors are associated with elevated levels of forebrain CRF and UI gene expression and with an activation of the hypothalamic-pituitary-interrenal (HPI) stress axis. In contrast, although stressors can also be associated with an increase in caudal neurosecretory system CRF and UI gene expression and an endocrine role for CRF-related peptides has been suggested, the physiological effects of peripheral CRF-related peptides on the gastrointestinal system and in the regulation of appetite have not been investigated. Overall, while CRF and UI appear to participate in the stress-induced changes in feeding behaviour in fish, the role of other know components of the CRF system is not known. Moreover, the extent to which the anorexigenic effects of CRF-related peptides are mediated through the hypothalamic feeding center, the HPI axis and cortisol, or via actions on descending autonomic pathways remains to be investigated.

Animals↗

Dopamine output in the nucleus accumbens shell is related to the acquisition and the retention of a motivated appetitive behavior in rats.

Chronic stress exposure consistently impairs the reactivity to aversive and pleasurable stimuli in rats; these behavioral modifications are associated with a decrease in dopamine output in the nucleus accumbens shell (NAcS). However, when rats that have already acquired an appetitive behavior are exposed to chronic stress, they develop an impaired reactivity to avoidable aversive stimuli while retaining the appetitive behavior. The dissociation between these two behavioral traits was used to study whether the decreased dopaminergic activity in the NAcS was connected to either of the two deficits. Dopamine output was studied through microdialysis as dopamine accumulation following re-uptake inhibition by cocaine. When rats that had previously acquired the appetitive behavior were exposed to chronic stress, they showed a dopaminergic transmission in the NAcS similar to that of controls and significantly higher than that of chronically stressed animals. Thus, dopamine output in the NAcS was consistently associated to the acquisition and maintenance of appetitive behavior, while the expression of a deficit in avoidance appeared to be independent of it.

Animals↗

Interaction between brain L-type calcium channels and alpha2-adrenoceptors in the inhibition of sodium appetite.

Calcium channels mediate the actions of many drugs. The present work investigated whether diltiazem, an L-type calcium channel blocker, alters the inhibition of sodium appetite induced by noradrenaline and the alpha2-adrenoceptor agonist clonidine. Adult male Holtzman rats (N=4-8) with cannula implanted into the third cerebral ventricle were submitted to sodium depletion (furosemide sc+24-h removal of ambiente sodium). Sodium depleted control animals that received 0.9% NaCl as vehicle injected intracerebroventricularly (i.c.v.) ingested 13.0+/-1.5 ml/120 min of 1.8% NaCl. Intracerebroventricular injection of either noradrenaline (80 nmol) or clonidine (20 nmol) inhibited 1.8% NaCl intake from 70 to 90%. Prior i.c.v. injection of diltiazem (6-48 nmol) inhibited from 50 to 100% the effect of noradrenaline and clonidine in a dose-response manner. Diltiazem alone at 100 nmol inhibited, but at 50 nmol had no effect on, sodium appetite. The results suggest: (1) common ionic mechanisms involving calcium channels for the inhibition that noradrenaline and clonidine exert on sodium appetite and (2) a dual role for the benzothiazepine site of L-type calcium channels in the control of sodium appetite.

Adrenergic alpha-Agonists↗

Decreases in neurokinin-3 tachykinin receptor-immunoreactive and -mRNA levels are associated with salt appetite in the deoxycorticosterone-treated rat.

Tachykinins are a family of neuropeptides that inhibit salt appetite. Although decreased tachykinin-mRNA levels are observed in natriorexic sodium-deplete rats, no decrease is seen in natriorexic sodium-replete rats that are administered the aldosterone-mimetic deoxycorticosterone acetate (DOCA). Since reduced synthesis of tachykinins could not account for increased appetite, we hypothesized that increased salt appetite was due to a downregulation of tachykinin receptors. Thus, we injected rats with DOCA once daily for 11 days and analyzed tachykinin receptor subtype, neurokinin 3 (NK3r)-immunoreactivity by Western blot analysis since intracerebroventricular injection of senktide (NK3r agonist) attenuates salt intake in DOCA-treated animals. We examined NK3r-immunoreactivity in several brain regions thought to be associated with the control of water and electrolyte balance including the bed nucleus of the stria terminalis, central nucleus of the amygdala, diagonal band of Broca, hippocampus, nucleus tractus solitarius, parabrachial nucleus, paraventricular nucleus of the hypothalamus, and supraoptic nucleus. Consistent with our hypothesis, we found decreased NK3r-immunoreactivity in all brain regions analyzed except for increases in the amygdala and no changes in the paraventricular nucleus of the hypothalamus. To examine whether DOCA's effects on NK3r synthesis are direct, we used differentiated N1E-115 neuroblastoma cells that express NK3r and treated them with a range of concentrations of DOCA and found a dose-dependent decrease in NK3r-mRNA abundance via Northern blotting. The present results suggest that the tachykinin receptors are downregulated after subchronic DOCA treatment and this finding is consistent with the hypothesis that suppressed inhibition of salt appetite as mediated through the tachykininergic system.

Animals↗

Stimulation of appetite by alcohol.

To investigate the effects of alcohol on appetite and food intake, 26 males attended the laboratory on three occasions. On each occasion, they were given a standard breakfast. Visual analog scale ratings of hunger, desire to eat and fullness (appetite ratings) were recorded from before breakfast until their return to the laboratory for lunch. Thirty minutes before lunch, subjects either rested (baseline), were given 330 ml of a no-alcohol lager (264 kJ: no-alcohol condition) or 330 ml of the same lager spiked with 3 units of alcohol (24 g ethyl alcohol; total energy=969 kJ: alcohol condition). Ratings of appetite were taken before and after the preload or baseline rest period and again before and hourly after lunch. The test meal at lunch consisted of a buffet-style array of foods and chilled water. Ad libitum intake at lunch (excluding energy from alcohol) was significantly higher following alcohol (7301+/-442 kJ) compared to both baseline (6365+/-334 kJ) and the no-alcohol conditions (6479+/-289 kJ). Appetite ratings failed to demonstrate any differences between alcohol and the no-alcohol condition. Total energy intake (including energy from alcohol) was enhanced in the alcohol condition by 30%, suggesting that energy from alcohol is not compensated in the short-term and may even have a stimulatory effect on food intake.

Adult↗

Deoxycorticosterone acetate (DOCA)-induced sodium appetite in group-housed mice.

Research investigating sodium hunger in mice has failed to produce evidence that mineralocorticoids are involved in sodium appetite. In our own laboratory, doses of deoxycorticosterone acetate (DOCA) ranging from 1 mg/kg to 20 mg/kg have failed to induce a sodium appetite. In rats, glucocorticoids have been effective in potentiating mineralocorticoid-induced sodium appetite. Recent research has suggested that the mouse, like the rat, does possess mineralocorticoid sensitivity for sodium hunger but, unlike the rat, has a strong dependency on an accompanying glucocorticoid action. The present experiment was conducted to study the effects of DOCA on sodium appetite in mice under housing conditions that attempted to eliminate the reduction of corticosterone associated with social isolation. Therefore, male GHSC mice were group-housed and were tested within two counterbalanced treatment conditions. One condition consisted of an injection of 10 mg/kg DOCA on 2 consecutive days, and the other condition consisted of an injection of the vehicle on 2 consecutive days. Group-housed male GHSC mice showed a significantly larger amount of NaCl consumption after injections of DOCA than after injections of the vehicle.

Animals↗

Comparison of the effects of a high-fat and high-carbohydrate soup delivered orally and intragastrically on gastric emptying, appetite, and eating behaviour.

To investigate the effects of fat and carbohydrate on appetite, food intake and gastric emptying with and without the influence of orosensory factors, a group of nine healthy, fasted male subjects took part in two separate paired experiments involving high-fat and high-carbohydrate radiolabelled soup preloads. In the first experiment subjects received direct intragastric isocaloric infusions of either a high-fat tomato soup or a high-carbohydrate tomato soup (400 kcal in 425 mL) over 15 min, on two occasions. In the second paired experiment subjects ingested the same high-fat and high-carbohydrate soup over 15 min. In both experiments ratings of hunger and fullness were recorded over a period of 135 min and gastric emptying was measured by scintigraphy. Food intake was evaluated from a test meal (yoghurt drink) given 2 h after the end of the soup infusion/ingestion. When soup was administered intragastrically (Experiment 1) both the high-fat and high-carbohydrate soup preloads suppressed appetite ratings from baseline, but there were no differences in ratings of hunger and fullness, food intake from the test meal, or rate of gastric emptying between the two soup preloads. When the same soups were ingested (Experiment 2), the high-fat soup suppressed hunger, induced fullness, and slowed gastric emptying more than the high-carbohydrate soup and also tended to be more effective at reducing energy intake from the test meal. The results of these studies demonstrate that orosensory stimulation plays an important role in appetite regulation, and also indicate that subtle differences in orosensory stimulation produced by particular nutrients may profoundly influence appetite and gastrointestinal responses.

Adult↗

Effect of beta-adrenergic antagonists on the spontaneous appetite for NaCl solution in rats.

Chronic dietary administration of the beta-adrenergic antagonist, propranolol (1.6-2.0 g/kg), to both male and female rats induced an appetite for 0.25 M NaCl solution when the rats were offered a choice between distilled water and salt solution to drink. Treatment was also accompanied by a significant reduction in both water and food intakes. In addition, increases in intake of NaCl solution during treatment with propranolol were correlated significantly with increases in urinary sodium output. To test for completeness of beta-adrenergic blockade, treated and control rats in the first study were administered isoproterenol (25 micrograms/kg b.w., SC) acutely and given only water to drink. The increased 1 hr water intake characteristically accompanying acute administration of isoproterenol was blocked completely by propranolol. Additional experiments were carried out with butoxamine, a selective beta 2-adrenoceptor antagonist, (1.5 and 3.0 g/kg of food) to determine its effect on intake of 0.25 M NaCl solution. Butoxamine failed to produce a significant effect on salt appetite. The results indicate that chronic treatment with propranolol, but not butoxamine, induces an appetite for NaCl solution. They further suggest, but do not prove, that beta 1-adrenoceptors may be involved in the appetite for NaCl solutions in rats.

Adrenergic beta-Agonists↗

The effects of phenytoin on instrumental appetitive-to-aversive transfer in rats.

Antiepileptic medications are the primary treatment for seizure conditions. Over the past several years, it has become clear that the medications themselves may contribute to the negative cognitive side effects that people with epilepsy often report. In the experiments reported here, the effects of phenytoin treatment have been evaluated in rats performing an instrumental appetitive-to-aversive transfer task. We find that rats treated with phenytoin fail to acquire the avoidance response when transferred from an appetitive to an aversive context. This deficit is not due to any sensory or motor slowing resulting from the drug, nor is it a deficit that is specific to learning in an aversive context. Rather, we suggest that the deficits shown by phenytoin-treated rats in the appetitive-to-aversive transfer reflect a fundamental inability in altering the associations that were formed during the initial appetitive training.

Animals↗

Motor control of the appetitive phase of feeding behavior in Aplysia.

The appetitive phase of feeding behavior, in the gastropod, Aplysia, consists of head lifting, head waving, orientation of the head to food, and locomotion. We have initiated studies of the neural control of head waving using three methods: (i) anatomical description of the nerves innervating muscles that are involved in head movement, (ii) electrical stimulation of nerves in a semi-intact preparation, and (iii) recording from nerves in free-moving animals. The muscles controlling head movements, located in the dorsal and lateral neck region, are innervated primarily by pleural nerve 1 and pedal nerves 2, 3, and 5. Electrical stimulation of these nerves caused both longitudinal and lateral contractions of the neck muscles, the largest contractions being in the area where the nerve first enters the muscle. Extracellular recordings from pleural nerve 1 and pedal nerves, in free-moving animals, showed an increase in extracellular activity during head lifting, at the onset of appetitive feeding behavior. Directionally specific inhibition and excitation in neural activity occurred in pleural nerve 1 and pedal nerve 5 during leftward and rightward movements of the head (head waving). Cobalt and nickel backfills of pleural nerve 1 and pedal nerve 5 revealed cell bodies in the cerebral, pedal, and pleural ganglia. The neurons are therefore putative motor neurons for the neck muscles involved in appetitive behavior. This evidence suggests that appetitive control of feeding may involve the coordinated activity of several different ganglia.

Animals↗

Appetite and weight change in patients presenting with depressive illness.

Appetite and weight in 193 moderately depressed outpatients who satisfied Feighner's criteria for a primary depressive episode were found to be strongly associated with previous appetite and weight history. There was no overall association between weight change and severity of depression, nor with the classical features of endogenous depression, such as early morning waking and morning worsening of mood. Appetite change in either direction was, however, associated with a more severe degree of depression on the Hamilton and Beck scales. Normal appetite changes in response to stress occur in an exaggerated way in this depressive illness.

Adult↗

Salt appetite of adrenalectomized rats after a lesion of the SFO.

Circumventricular organs such as the subfornical organ (SFO) may mediate the effects of circulating angiotensin (ANG) II on salt appetite under conditions of sodium depletion in the rat. We studied the effects of an electrolytic lesion of SFO on salt appetite after adrenalectomy (ADX) in Long-Evans rats. The SFO lesion had no effect on saline intake, but it did abolish water intake after acute peripheral treatments with 2 mg/kg of captopril or a 10 mg/kg of furosemide. These findings contrast with other recent data from this laboratory demonstrating large reductions in salt appetite in adrenal-intact rats with lesions of either SFO or the organum vasculosum laminae terminalis during acute iv infusions of ANG II. Thus, the SFO may contribute to the salt appetite response to circulating ANG II, but it is not essential for the response to adrenalectomy.

Adrenalectomy↗

Relation between appetite ratings before and after a standard meal and estimates of daily energy intake in obese and reduced obese individuals.

The aim of the present study was to relate appetite ratings before and after a standard breakfast to estimates of daily energy intake, before and after weight loss obese men and women. Nineteen obese subjects (9 men and 10 women) took part in a 15-week drug-based weight-loss program coupled to energy intake restriction. Body weight and body composition were significantly decreased in men and women. Both before and after the weight loss program, desire to eat, hunger, fullness and prospective food consumption (PFC) were measured after an overnight fast and at 10-min intervals in the hour following the ingestion of a standardized breakfast. Energy intakes were also measured and reported before and after weight loss. Fasting desire to eat and postprandial area under the curve (AUC) for hunger were significantly increased (p<0.05) after the intervention. No association was observed between measured or reported energy intakes and appetite ratings before weight loss in either men or women. Reported energy intake was not associated with appetite sensations after weight loss either. In contrast, measured energy intake was significantly associated with postprandial AUC for fullness (r=-0.90, p<0.01) and PFC (r=0.80, p<0.01) in men at the end of the program. In stepwise multiple regression analysis, only postprandial AUC for PFC contributed independently to the variance of measured energy intake after weight loss (r(2)=0.60, p=0.01). This study did not show consistent associations between averaged appetite ratings after a meal and daily energy intake, either before or after weight loss.

Adult↗

Increased sodium appetite stimulates c-fos expression in the organum vasculosum of the lamina terminalis.

The relation between c-fos expression in the forebrain of Lister hooded rats and water and NaCl intakes was examined in response to systemic injection of angiotensin II, desoxycorticosterone, angiotensin II and desoxycorticosterone together, frusemide or low sodium diet, all treatments that induce a sodium appetite. Angiotensin II (1 mg/kg subcutaneously) caused significant increases in the 1-h intakes of water and 1.8% NaCl compared to controls, the effect on water intake being the greater. There was a similar increase in NaCl intake after four days' treatment with desoxycorticosterone (20 mg pellet subcutaneously) but water intake was not increased. The NaCl intake of rats given angiotensin II following desoxycorticosterone treatment was approximately the sum of the intakes after angiotensin II or desoxycorticosterone alone, but the water intake was slightly less than after angiotensin II alone. Frusemide pretreatment (4 mg/kg subcutaneously) caused an NaCl intake similar to that following angiotensin II and desoxycorticosterone but water intake was little affected. Low dietary sodium also increased salt appetite, as expected. These treatments were repeated in rats that were not allowed to drink NaCl, after which the brains were processed for c-fos immunocytochemistry. This showed intense staining of the subfornical organ, median preoptic nucleus, organum vasculosum of the laminal terminalis, paraventricular nucleus and supraoptic nucleus after subcutanous angiotensin II. Animals given angiotensin II following desoxycorticosterone pretreatment showed patterns of c-fos expression that did not differ from those of angiotensin II alone. Treatment with desoxycorticosterone alone produced intense staining in the organum vasculosum of the laminal terminalis and some staining in the median preoptic nucleus. Frusemide gave a similar pattern of staining to desoxycorticosterone, stimulating c-fos expression in the same regions but to a lesser extent. A low salt diet resulted in increased c-fos expression only in the organum vasculosum of the laminal terminalis. Therefore, five different treatments that induced increased sodium appetite evoked distinct patterns of c-fos expression in the anteroventral region of the third ventricle of the rat forebrain. Since the common feature was induction of c-fos in the organum vasculosum of the laminal terminalis, these results suggest a key role for this structure in the development of increased sodium appetite.

Angiotensin II↗