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Food intake and the menstrual cycle: a retrospective analysis, with implications for appetite research.

The biological regulation of appetite is currently an important topic in nutrition, since hyperphagia has been implicated as the prime cause of obesity. Cyclical fluctuations in food intake occur in women across the menstrual cycle, with a periovulatory nadir and a peak in the luteal phase. These alterations in food intake, in response to ovarian steroid hormone changes may be more than 2.5 MJ/day, with the mean reported changes shown in 19 separate studies of 1.0 MJ/day. Hormonal induced fluctuations in food intake could, therefore, contribute to energy imbalance and consequent weight gain. Further, in nutrition studies involving women subjects where the menstrual cycle phase is not controlled, hormonally induced changes in food selection and intake may mask the often considerably smaller changes in response to experimental variables in appetite research.

Appetite↗

Strategies for investigation of CNS mechanisms of phenotypic variation in blood pressure and salt appetite in genetic hypertensive rats.

Several characteristics of spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY), make these homozygous strains particularly well suited for investigating the interactions of salt appetite, blood pressure control, and their neuroendocrine substrates. Appropriate genetic and developmental investigations of sources of variation in salt appetite, blood pressure, and their putative neuroendocrine substrates in these homozygous strains can provide valuable insights into fundamental mechanisms of disease, as well as factors controlling homeostatic behavioral and physiological processes. However, inappropriate use of these strains can produce misleading, although seductively plausible, conclusions regarding mechanisms. Selective inbreeding for hypertension has concentrated in SHR the "high pressure" allele for several genes that influence blood pressure, whereas breeding for normal blood pressure has left WKY with the "normal pressure" allele for all or most of these genes. In principle, inbred hypertensive strains could provide information about specific genetic alterations that mediate the hypertensive phenotype. The benefits of work with these strains are discussed, but several false assumptions and logical pitfalls are described that might cause misleading or erroneous interpretations of results from work with such strains. These problems illustrate the importance of the research strategy in elucidating the particular information that can be provided by these inbred animal models of hypertension. Two strategic approaches for studying hypertension and other genetically determined or influenced characteristics in inbred animal models such as SHR are discussed: cosegregation analysis for identifying or rejecting genetic linkage, and brain graft techniques for identifying brain specific genetic influences on cardiovascular or behavioral phenotypes. Examples of each approach are described.

Animals↗

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)-induced appetite suppression in the Sprague-Dawley rat is not a direct effect on feed intake regulation in the brain.

The most striking sign of acute toxicity of TCDD in animals is a progressive reduction of feed intake, accompanied by loss of body weight eventually resulting in death. The mechanism(s) of this voluntary feed refusal is (are) not known but it is generally accepted that both centrally and peripherally (via feedback) acting anorectic agents exert their effect(s) in the hypothalamus. In this study direct administration into the lateral cerebral ventricle of rats resulted in much higher concentrations of TCDD in the hypothalamus and also in other regions of the brain than after a lethal intravenous (iv) injection. While rats injected iv displayed the expected cachectic syndrome, intracerebroventricularly (icv)-dosed animals ate and gained weight normally. These findings preclude the possibility of a direct effect of TCDD on appetite-regulating areas of the brain. Moreover, these results require the assumption that the appetite suppressive effect of TCDD is due to a (feedback) mechanism originating in the periphery.

Animals↗

Biological bases for the integration of appetitive and consummatory grooming behaviors in the cat: a review.

Cats with pontile lesions, frontal neocortical lesions, and thyroidectomized cats display a dissociation of the appetitive and consummatory components of grooming behavior following tactile stimulation of the body surface, an abnormal behavior which waxes and wanes with the seasons of the year. Tryptophan hydroxylase activity and serotonin levels were significantly decreased in the superior colliculi (but not other brain regions) in cats with pontile lesions or frontal neocortical lesions, but not in thyroidectomized cats. Systemic administration of 5-hydroxytryptophan or monoamine oxidase inhibition plus tryptophan administration abolishes the abnormal grooming behavior in each group of cats, and microinjections of 5-hydroxytryptophan or serotonin into the superior colliculi has the same effect, indicating that the change in a serotonergic system is a critical aspect of the abnormal behavior in cats with lesions and that a serotonergic system may also be involved in the genesis of the abnormal grooming behavior in thyroidectomized cats. Functional inactivation of the serotonergic system by p-chlorophenylalanine, LSD, or serotonin receptor blockade does not induce the abnormal grooming behavior in normal cats, indicating that other factors are involved. Cats with lesions and thyroidectomized cats display a rhythmic dysfunction in the excretion of glucocorticoids and glucocorticoid administration abolishes the abnormal grooming behavior, suggesting that glucocorticoids are the other critical factor. Adrenalectomized cats do not display the abnormal grooming behavior, but when adrenalectomized cats are treated with p-chlorophenylalanine, the abnormal behavior appears. Thus, a serotonergic system in the superior colliculi, operating at some level of glucocorticoid function, is involved in the integration of appetitive and consummatory grooming behaviors.

5-Hydroxytryptophan↗

ACTH induced sodium appetite in the rat.

Subcutaneous injections of long-acting synthetic ACTH (5 U/day) caused a large increase in the intakes of both 0.5 M NaCl and water in rats. By the fifth day of treatment the rats were turning over an amount of sodium approximating their own total body sodium. The mineral appetite was specific for NaCl. Intakes of KCl, MgCl2 and CaCl2 were unchanged. ACTH was ineffective in adrenalectomized rats suggesting that the appetite was dependent on adrenal hormones.

Adrenalectomy↗

Long-term treatment of obese Zucker rats with LY255582 and other appetite suppressants.

LY255582, administered subcutaneously, decreased food intake and body weight gain of fed obese Zucker rats during the entire 30-day period of treatment. No tolerance to these biologic effects of LY255582 could be demonstrated. d-Amphetamine and naltrexone, administered subcutaneously, and d,l-fenfluramine and salbutamol, administered orally, decreased food intake for no more than 6 to 12 days, in contrast to the long-lasting effects of LY255582. Salbutamol suppressed the appetite of obese rats for 3-4 days only. After an additional 12 days of treatment, weight gain decreased significantly accompanied by no appetite suppression. Thus, there is a difference in the duration of action of the opioid antagonist, LY255582, when compared to amphetamine, fenfluramine, naltrexone, and salbutamol, on food intake and body weight gain of obese rats.

Albuterol↗

Effects of post-training ethanol and group housing upon memory of an appetitive task in mice.

It has been shown that post-training ethanol's facilitating effects upon memory disappeared if the mice were kept isolated after training. Since ethanol-treated mice were attacked by their cagemates, it has been hypothesized that the improved retention induced by ethanol resulted from an interaction between ethanol and group housing which added aversive information to training. To investigate the correctness of this interpretation, ethanol effects upon memory of an appetitive task were studied. C57BL/6J mice (isolated the day before training) were individually trained to find a cheese pellet placed in a corner of an open-field. Mice were injected intraperitoneally immediately after training with saline, 0.5, 1.5, or 2.0 g/kg of ethanol. They were then returned to their home cage and left alone, with another mouse, or with five other mice for 2 h after training. All mice were tested 24 h later for retention. Reductions in the number of pellet approaches or in the latency to eat the pellet were taken as measures of learning. Post-training ethanol disrupted retention of the appetitive task in a dose-related manner. Moreover disruption was greater in mice group housed after training. The results support the hypothesis that ethanol's post-training facilitating effects upon aversive memory may be due to added aversive information to the stimulus complex, rather than, or in addition, to enhanced storage of memory traces.

Animals↗

Gamma-L-glutamyl-L-aspartate, interacting with NMDA receptors, affects appetitive visual discrimination tasks in mice.

gamma-L-glutamyl-L-aspartate (gamma-LGLA), which interacts with NMDA receptors, has been shown to impair retention of an active avoidance task in mice. Here, we specified the behavioral effects of gamma-LGLA on acquisition and retention of appetitive nondelayed visual discrimination tasks. Three experiments were conducted: the peptide (0.25 and 2.5 microM/kg/25 ml. ip) was administered 3 min after each of the first six sessions of either original learning, reversal 1 or reversal 3. gamma-LGLA affected acquisition of the original task and of the first reversal, as revealed by an absence of improvement on initial sessions and an increased number of sessions to reach criterion fixed at 7 of 10 correct choices on three consecutive sessions. This deficit did not result from an action of the peptide on position habits (repetition of spatial choices) nor on motivational processes, suggesting a specific interference of gamma-LGLA with acquisition and memorization of the visual rule. In contrast, gamma-LGLA had no effect on acquisition of the third reversal, in which the positively reinforced visual stimulus was identical to that used on the first reversal. These results show that the behavioral deficits of gamma-LGLA, which had previously been demonstrated in an aversive task, can be generalized to appetitive tasks based on acquisition of a new rule.

Animals↗

Increased sodium appetite and thirst in rat induced by the ingredients of liquorice, glycyrrhizic acid and glycyrrhetinic acid.

In the rat, blocking 11 beta-OHSD with the active ingredient of liquorice, glycyrrhizic acid (GZA) or its hydrolytic product, 18 beta-glycyrrhetinic acid (GTA), caused potassium loss, increased water intake and a primary increase in salt appetite that was specific for sodium and not secondary to sodium loss. Intracerebroventricular injection of angiotensin II enhanced the sodium appetite but carbachol did not. The stimulating effects of GZA or GTA on intakes of water and NaCl resembled those caused by the administration of excessive amounts of mineralocorticoid. The results suggest that GZA- or GTA-induced drinking behaviour is mediated by circulating glucocorticoids. After liquorice blockade of 11 beta-OHSD, the peripheral and central mineralocorticoid receptors are no longer protected from glucocorticoid action.

Angiotensin II↗

The role of angiotensin II in ingestive behaviour: a brief review of angiotensin II, thirst and Na appetite.

From the outset, the study of angiotensin II (Ang II) in body fluid homeostasis has been both complicated and intriguing. Since the publication of an early report of the dipsogenic action of this peptide, the pursuit of the role of Ang II in thirst and Na appetite has continued for the last 25 years. This pursuit captured the attention of all workers interested in the behavioural/physiological regulation of body fluid balance, with major contributions being made by James T. Fitzsimons and his colleagues. In spite of its powerful dipsogenic actions, delineation of its precise role in physiological thirst has been elusive and difficult to demonstrate. The influence of Ang II on Na intake took longer to show convincingly. However, in contrast to thirst, the role of Ang II in physiological Na appetite has been demonstrated clearly. The technological advances made during the recent years have greatly increased our ability to delineate the neurobiological context of Ang II-mediated responses. Thus, the future is promising in regard to illuminating the subtleties of the role of Ang II in body fluid balance.

Angiotensin II↗

Sodium appetite and cerebrospinal fluid sodium concentration during hypovolemia.

A lowered concentration of sodium in the cerebrospinal fluid (CSF) has been suggested as a critical signal for the elicitation of sodium appetite. This was evaluated in naive male Long-Evans rats made hypovolemic by subcutaneous injection of the colloid polyethylene glycol (PEG) in a hyperoncotic concentration. At 2, 5 or 8 h after PEG or vehicle injection, under conditions of availability or non-availability of water and 0.3 M NaCl for ingestion, the rats were anesthetized and samples of CSF and blood were taken. Water intakes of the PEG treated rats were elevated at 5 and 8 h, and 0.3 M NaCl intakes were elevated at 8 h in comparison to vehicle treated rats. When fluids were not available, CSF sodium concentrations were greater in PEG than in vehicle treated rats at 2, 5 and 8 h. When fluids were available, CSF sodium concentrations were greater in PEG than in vehicle treated rats at 5 and at 8 h. There was no correlation between CSF sodium concentration and saline intake. In summary, a lowered CSF sodium concentration is not a necessary condition for sodium appetite in the hypovolemic rat.

Animals↗

Perception of appetite and weight change during treatment for depression.

As part of the Pittsburgh Appetite Test, 50 depressed outpatients reported their perceptions of appetite and weight change prior to and during chronic treatment with imipramine and psychotherapy. At the end of 4 months, as a group, patients were significantly more conscious of what they were eating, and reported a significant change in the frequency of regular meal consumption. No group changes were noted in frequency of snacking or late night eating, although weight change during treatment and obesity status modified these responses. Clinical response was unrelated to eating behavior. Perception of weight change varied with treatment: a 5 pound weight gain became highly problematic during recovery compared to the depressive episode. The interaction of these factors and antidepressant-induced weight gain are discussed.

Adult↗

Hunger and appetitive factors during total parenteral nutrition.

A previous study of short-term (average of 31 days) Total Parenteral Nutrition (TPN) patients indicated that they experienced hunger even though they received adequate calories for energy balance. A prolonged suppression of hunger was noted when lipid was added to the total nutrient intake. Recent experiments with intravenous infusion of lipids in normal volunteers have failed to show appetite suppression beyond that expected from caloric regulation. The goal of our study was to collect information regarding hunger and appetitive experiences associated with intravenous alimentation of healthy, long-term, home TPN patients. Our results from questionnaire returns of 29 respondents showed hunger to be generally low during most of the day. Those patients taking small amounts of food orally typically reported moderate hunger before eating. There was no evidence of any significant difference between hunger reports given on days when lipid was infused vs. days when lipid was omitted. Aversive sensations were frequently associated with lipid infusion but not with nonlipid nutrient infusion. Hunger in TPN patients is discussed in terms of expectancy and hedonic factors as contrasted with physiological need.

Adult↗

Dopamine functions in appetitive and defensive behaviours.

The data reviewed here are compatible with the hypothesis that telencephalic dopamine activity is elicited by motivationally significant stimuli which in turn creates a neural state in which animals are more prepared to respond to significant stimuli in the environment. This analysis may be viewed as extensions of both the sensorimotor hypothesis, which depicts dopamine as potentiating the ability of stimuli to elicit responses (Clody and Carlton, 1980; Marshall et al., 1974; White, 1986) and of the incentive motivational hypothesis, which emphasizes the importance of dopamine in responding to stimuli that serve as signals of biologically significant events (Blackburn et al., 1989a; Crow, 1973; Mogenson and Phillips, 1976). In addition, we have sought to emphasize that not all responses are equally dependent upon the integrity of forebrain dopamine activity. Some responses, such as ingestion of standard foods by hungry animals, copulation, and escape, are relatively impervious to dopamine disruption. Further, once other behaviours, such as avoidance or appetitive operant responses, have been acquired, they can be maintained at an initially high rate despite perturbation of dopamine systems, although performance deteriorates with repeated testing. This analysis has emerged from the joint consideration of how both appetitive and defensive behaviours are influenced by dopamine antagonists, along with an examination of dopamine release during sequences of behaviour. The data reviewed suggest that dopamine is involved in fundamental psychological processes through which environmental stimuli come to exert control over certain aspects of behaviour. In the future, as knowledge in this field advances, there will have to be an integration of the literature on dopamine and motivation with the literature on dopamine and motor systems. We expect that dopamine release will be seen as a mechanism by which important environmental cues, of innate or learned significance, lead to a general enhancement of motor skeletal responses directed towards distal cues. We conclude with a caveat: Caution must be exercised when attempting to infer a general role of any neurotransmitter in motivated behaviour based on the study of a limited number of motivational systems. Although neurotransmitter pathways may figure prominently in the control of certain behaviours, it is incorrect to think of neurotransmitters as having a single role in behaviour. However, when comparative analyses reveal a common thread among different motivational systems, as is becoming apparent for the general role of mesotelencephalic dopamine pathways in behaviour, then the goal of generating coherent and comprehensive theory concerning a neurotransmitter's function in behaviour will begin to be realised.(ABSTRACT TRUNCATED AT 400 WORDS)

Aggression↗

The tachykinin NH2-senktide, a selective neurokinin B receptor agonist, is a very potent inhibitor of salt appetite in the rat.

The tachykinin peptide [Asp5.6, MePhe8]substance P(5-11) (NH2-senktide), a senktide analogue lacking the N-terminal succinyl group, is a selective and metabolically stable NK-3 receptor agonist. In the present study it potently inhibited salt appetite induced by sodium depletion in rats. Argo-neurokinin B, too, inhibited salt appetite, but was less potent than NH2-senktide. Neither peptide inhibited drinking behaviour induced by subcutaneous hypertonic NaCl. NH2-senktide slightly inhibited angiotensin-induced drinking, while Argo-neurokinin B was ineffective. On the other hand, eledoisin was a potent inhibitor in the 3 behavioural tests. Present results indicate that activation of NK-3 receptors is involved in the antinatriorexic action of tachykinins, and that different receptor subtypes might be involved in the different effects of tachykinins on the rat ingestive behaviour.

Animals↗

Promotion of hepatic lipid oxidation and gluconeogenesis as a strategy for appetite control.

There is considerable evidence that hepatic vagal afferents monitor the availability of liver glycogen and glucose metabolites, and that this mechanism participates in appetite regulation. Thus, promotion of gluconeogenesis and liver glycogen storage may enhance satiety. Hepatic lipid oxidation drives gluconeogenesis by positive allosteric modulation of pyruvate carboxylase and fructodiphosphatase. The rate-limiting enzyme for hepatic lipid oxidation, carnitine acyltransferase I, is activated by exogenous carnitine, and inhibited by malonyl coA. The lipogenesis inhibitor (-)-hydroxycitrate--a natural fruit acid found in the Brindall berry--can decrease production of malonyl coA in hepatocytes by potent inhibition of citrate lyase; many studies demonstrate that (-)-hydroxycitrate can reduce body fat accumulation in growing rats, owing in large part to a reduction in appetite. Joint administration of (-)-hydroxycitrate and carnitine should therefore promote hepatic lipid oxidation, gluconeogenesis, and satiety. Thermogenic effects as well as a reduction of the respiratory quotient can also be predicted. If this technique proves clinically useful in weight management, it could be used in conjunction with chromium picolinate and soluble fiber supplements, which appear to aid hunger control at the level of the hypothalamus and terminal ileum, respectively.

Animals↗

Re-examination of the effect of either a lateral or third ventricular cannula on captopril-induced salt appetite in rats.

In Study A, rats were implanted with a cannula aimed at either the lateral (LV) or ventral third (V3V) brain ventricles 1 week prior to starting a chronic oral regimen of captopril. The presence of neither cannula significantly impaired the emergence of captopril-induced appetite for NaCl solution. In Study B, V3V cannulae were implanted in rats after a captopril-induced appetite for NaCl was established. The surgery produced a 1-2 day attenuation of NaCl intake, but this was no greater than that observed in a sham-operated group that received no cannula. These results do not support those of others who suggest that captopril (and, by inference, other agents) can leak across a damaged blood-brain barrier for at least 2 weeks after placement of a cannula. Possible reasons for the differences in results are addressed.

Administration, Oral↗

Appetite and taste preference in growing rats given various levels of protein nutrition.

The cephalic gustatory stimuli during a meal yield nutritional information and aid in the efficient control of homeostasis. This study was focused on either appetite for flavored food or feeding behavior in growing male Sprague-Dawley rats under various states of protein nutrition. In fasted rats, endogenous protein degradation was suppressed by ingestion of glucose that was sufficient to meet energy needs. The decrease in the amount of diet intake was compensated by sugar ingestion, except for sucrose. Rats that ingested sucrose exceeded 115% of total energy intake, compared to ingestion of saccharin as a control. Appetite and meal size are primarily dependent upon the dietary protein level, whether it was beyond normal requirements or not and, thus, flavoring by certain taste material is effective for a diet sufficient in protein, but not for a deficient one. In addition, rats fed a diet containing amino acids preferred saccharin and monosodium L-glutamate (MSG) and grew normally. But, when L-tryptophan-deficient diet was offered, the preference for tryptophan was elicited, and then MSG intake was elevated and their growth became normal. However, preference for saccharin never occurred because the level of tryptophan in blood fluctuated and was not maintained within normal limits. The strong preference for sweetness that is evoked by starvation is directly regulated by the negative energy balance. The animals' primary concern was energy intake and their second concern was protein nutrition, regardless of flavoring.

Aging↗