Appetitive States Research Articles

Ventral Pallidum Firing Codes Hedonic Reward: When a Bad Taste Turns Good

The ventral pallidum (VP) is a key structure in brain mesocorticolimbic reward circuits that mediate "liking" reactions to sensory pleasures. Do firing patterns in VP actually code sensory pleasure? Strong evidence for hedonic coding requires showing that neural signals track positive increases in sensory pleasure or even reversals from bad to good. A useful test is the salt alliesthesia of physiological sodium depletion that makes even aversively intense NaCl taste become palatable and "liked." We compared VP neural firing activity in rats during aversive "disliking" reactions elicited by a noxiously intense NaCl taste (triple-seawater 1.5 M concentration) in normal homeostatic state versus in a physiological salt appetite state that made the same NaCl taste palatable and elicit positive "liking" reactions. We also compared firing elicited by palatable sucrose taste, which always elicited "liking" reactions in both states. A dramatic doubling in the amplitude of VP neural firing peaks to NaCl was caused by salt appetite that matched the affective switch from aversive ("disliking") to positive hedonic ("liking") reactions. By contrast, VP neural activity to "liked" sucrose taste was always high and never altered. In summary, VP firing activity selectively tracks the hedonic values of tastes, even across hedonic reversals caused by physiological changes. Our data provide the strongest evidence yet for neural hedonic coding of natural sensory pleasures and suggest, by extension, how abnormalities in VP firing patterns might contribute to clinical hedonic dysfunctions.

Konorski and conditional reflexes: a historical summary and an addendum.

There have been four major pioneers from Eastern Europe in the neuroscientific study of memory and learning: Pavlov, Bekhterev, Beritashvili and Konorski. The thinking of each evolved with the progress of neuroscientific knowledge throughout the world, and save for Pavlov, each encountered governmental opposition to their views. Among the clues largely overlooked in their examination of conditional reflexes was the fact that the animal appreciates not only its own appetitive state but its immersion in the experimental setting. The latter in itself must require considerable, ongoing neuronal activity to sustain it. There is also the question as to whether "motivation" is an essential feature for the formation of conditional connections; and in cases where it is seemingly absent, as in recognition memory, the processes that underlie the astonishing efficacy of such memory formation remain almost wholly obscure. Finally, it is remarked that the cerebral cortex, as initially supposed, may indeed be the governing locus, even of such simple effects as habituation.

Carbachol injections into the nucleus accumbens induce 50 kHz calls in rats

In rats, different types of vocalization can be observed. High frequency vocalizations (so called 50 kHz calls) are believed to indicate an appetitive state of the emitting animal. This is supported by studies demonstrating that infusions of the dopamine agonist amphetamine into the nucleus accumbens (NAC), a key structure for appetitive behaviors, induce 50 kHz calls. Several studies during the last years demonstrated that not only infusions of dopamine agonists such amphetamine but also infusions of acetylcholine receptor agonists into the NAC stimulate the appetitive system. In present study, we tested whether infusions of the unspecific cholinergic agonist carbachol into the NAC are able to induce 50 kHz calls. Indeed, we observed a high number of 50 kHz calls after intra-NAC infusions of carbachol. The main frequency of the these calls was between 40 and 70 kHz, and the duration was mainly between 10 and 50 ms. We hypothesize that acetylcholine transmission within the NAC plays an important role in the induction of those ultrasonic calls indicating an appetitive state.

Amphetamine-induced 50 kHz calls from rat nucleus accumbens: A quantitative mapping study and acoustic analysis

Emission of 50 kHz ultrasonic calls in rats is known to be associated with appetitive behavioural situations and positive social interactions. The purpose of the study was to pharmacologically characterize amphetamine-induced 50 kHz calls and to perform quantitative mapping of this response in the nucleus accumbens. Injections of amphetamine into the nucleus accumbens induced species-typical 50 kHz calls in adult rats. The acoustic parameters of the calls were not affected by different amphetamine doses or combination of agents. The increase in the number of calls occurred predominantly from the accumbens shell and to a lesser degree from the core region. This effect was dose-dependent within the range of 1–20 μg of amphetamine and was reversed by pretreatment with D 1 or D 2 dopamine antagonists (SKF-83566 or raclopride) administered to the same brain site. However, another D 2 dopamine receptor antagonist, haloperidol, which is known to increase the accumbens dopamine level, was ineffective in reversing the increase in call number at the dose studied. On the contrary, intraacumbens haloperidol, when injected alone, caused an increase in 50 kHz calls. It is concluded that the release of dopamine, predominantly in the accumbens shell region, is responsible for production of 50 kHz calls and the calls may indicate an appetitive state compatible with anticipation of reward and positive affect. Both D 1 and D 2 subtypes of dopamine receptors may be necessary to induce 50 kHz calls and signal the appetitive state.

Fighting Strategies in Crayfish Orconectes rusticus (Decapoda, Cambaridae) Differ with Hunger State and the Presence of Food Cues

Crayfish, bearing dangerous weapons in the form of chelae, resolve intraspecific conflicts using stereotyped behaviors and structured, escalated encounters. According to predictions of game theory models, any decision to resort to unrestrained combat without prior careful behavioral assessment of the opponent’s fighting abilities carries great risks. The present study examines the significance of internal hunger states and the presence of chemical food cues in this decision process using a 2 × 2 factorial design. Hungry crayfish escalated more rapidly, and thus took greater risks, during agonistic encounters, while the presence of a food source reduced the rate at which fights increased in intensity. However, there were no significant differences in fighting behavior as a result of the interaction between these two variables. We then address the complex trade‐offs that individuals face in fighting with respect to increased risks of injury, appetitive states, and opportunities for resource access.

A novel technique to demonstrate disturbed appetite profiles in haemodialysis patients.

Malnutrition is common among dialysis patients and is associated with an adverse outcome. One cause of this is a persistent reduction in nutrient intake, suggesting an abnormality of appetite regulation. We used a novel technique to describe the appetite profile in 46 haemodialysis (HD) patients and 40 healthy controls. The Electronic Appetite Rating System (EARS) employs a palmtop computer to collect hourly ratings of motivation to eat and mood. We collected data on hunger, desire to eat, fullness, and tiredness. HD subjects were monitored on the dialysis day and the interdialytic day. Controls were monitored for 1 or 2 days. Temporal profiles of motivation to eat for the controls were similar on both days. Temporal profiles of motivation to eat for the HD group were lower on the dialysis day. Mean HD scores were not significantly different from controls. Dietary records indicated that dialysis patients consumed less food than controls. Our data indicate that the EARS can be used to monitor subjective appetite states continuously in a group of HD patients. A HD session reduces hunger and desire to eat. Patients feel more tired after dialysis. This does not correlate with their hunger score, but does correlate with their fullness rating. Nutrient intake is reduced, suggesting a resetting of appetite control for the HD group. The EARS may be useful for intervention studies.

Nucleus accumbens amphetamine microinjections unconditionally elicit 50-kHz ultrasonic vocalizations in rats.

The authors have hypothesized that, in adult rats, 50-kHz ultrasonic vocalizations (USVs) index a state characterized by high arousal and expectations of reward. This study was conducted to investigate whether dopamine agonism of the nucleus accumbens (NAcc) could evoke such an appetitive state, by examining the effects of NAcc amphetamine (AMPH) microinjections on USVs. Intra-NAcc AMPH injections (0.3, 1.0, 3.0, 10.0 microg unilaterally) produced robust, dose-dependent increases in 50-kHz USVs, which could not be accounted for by concomitant increases in locomotor activity (LA). However, AMPH injections into dorsal control caudate putamen sites produced a modest, dose-dependent increase in LA without significant increases in 50-kHz USVs. These findings indicate that NAcc AMPH microinjections selectively evoke 50-kHz USVs in rats, supporting the notion that dopamine elevations in the NAcc may unconditionally elicit a state of reward anticipation.

Predicting Hunger: The Effects of Appetite and Delay on Choice

Preferences often fluctuate as a result of transient changes in hunger and other visceral states. When current decisions have delayed consequences, the preferences that should be relevant are those that will prevail when the consequences occur. However, consistent with the notion of an intrapersonal empathy gap (Loewenstein, 1996) we find that an individual's current state of appetite has a significant effect on choices that apply to the future. Participants in our study made advance choices between healthy and unhealthy snacks (i.e., fruit and junk food) that they would receive in 1 week when they were either hungry (late in the afternoon) or satisfied (immediately after lunch). In 1 week, at the appointed time, they made an immediate choice, an opportunity to change their advance choice. Our main predictions were strongly confirmed. First, advance choices were influenced by current hunger as well as future hunger: hungry participants chose more unhealthy snacks than did satisfied ones. Second, participants were dynamically inconsistent: they chose far more unhealthy snacks for immediate choice than for advance choice. An additional hypothesis related to gender differences was also confirmed.

How can adaptive behavioural plasticity be implemented in the mammalian brain?

The adaptive control of behaviour requires brain mechanisms for the selection (i.e. activation and suppression) of responses, as well as mechanisms for the modulation of the response vigour. The concept of motivation postulates the existence of brain centres that regulate the selection and strength of behavioural responses. The present paper provides examples from the behavioural neurosciences for brain mechanisms that lead to adaptive changes of an organisms responsiveness to external stimuli. The mammalian startle response is a simple defensive behaviour which is mediated by an oligosynaptic pathway located in the lower brainstem. The startle response is enhanced by aversive states (fear, anxiety) and attenuated by appetitive states (pleasure), which can be regarded as an example of motivational priming. Furthermore, the startle response is inhibited by a weak sensory stimulus presented shortly before the startling stimulus. The suppression of startle by a prepulse is an example of sensorimotor gating, a principle that is important for the hierarchical organisation of behaviour. This paper describes the neuronal mechanisms underlying the modulation (prepulse inhibition and fear potentiation) of the startle response in rats, and discusses the possible adaptive significance of these different phenomena of behavioural plasticity.

Peripheral angiotensin causes salt appetite in rats.

The prevailing theory of sodium depletion-induced salt appetite states that angiotensin (ANG) of cerebral origin, not of renal origin, causes the behavior. This assertion depends partly on an experiment that suppressed salt appetite using an intravenous infusion of a dose of angiotensin-converting enzyme (ACE) inhibitor (captopril, 2.5 mg/h) that supposedly blocked both central and peripheral enzyme (17). The present experiments used the same dose of captopril to suppress salt appetite both in 24-h and in 3-h models of sodium depletion-induced behavior. The captopril-infused rats 1) increased water intake normally after central injections of ANG I given immediately after each salt appetite test, 2) had no arterial pressor response after intravenously injected ANG I, and 3) had normal arterial pressor responses after either intravenously injected ANG II or centrally injected ANG I. Thus, although the peripheral ACE was completely blocked in captopril-infused rats, the central ACE was not, because the central thirst and arterial pressor responses to ANG I were indistinguishable from controls. This demonstrates that ANG of renal origin is necessary for the expression of sodium depletion-induced salt appetite.

Drugs for Cocaine Dependence: Not Easy-Reply

In Reply.— Not easy, but consider the context. Hollister et al raise an important issue regarding the assessment of pharmacotherapeutic agents for cocaine dependence—whether cocaine craving is an appropriate surrogate outcome measure of cocaine use in inpatient studies. In our experience, and that of other researchers, 1 craving for cocaine declines fairly rapidly when cocaine-addicted individuals are sequestered as inpatients. Yet, on return to their former drug-using environments, a large percentage of these same patients may experience intense cravings and relapse. 2 These observations are consistent with a conditioning model of relapse: cues associated with previous cocaine use elicit cocaine-associated appetitive motivational states which, in turn, give rise to drug-seeking behavior. 3 The ability of a given pharmacologic agent to deflect these context-sensitive motivational states, both acutely and over the course of treatment, may be an important determinant of its effectiveness in the treatment of cocaine addiction. 4,5 This will be

Effects of atherosclerosis on mean and daily variation of arterial pressure in conscious WHHL rabbits.

Effects of atherosclerosis on the mean value and daily variation of arterial pressure were studied in 12 Watanabe-heritable hyperlipidemic (WHHL) rabbits aged 12 to 35 months and 25 normal Japanese white rabbits aged 6 to 30 months. A pressure catheter was inserted through the left subclavian artery under pentobarbital anesthesia. A few days after the catheterization, the mean arterial pressure (MAP) of the rabbits, which were active and in a good state of appetite, was recorded by an analogue-to-digital converter every second for about 6 hrs and stored in a computer. The mean (M) and standard deviation (SD) in the WHHL rabbit, calculated from each successive MAP record, ranged widely from 85.8 to 131.4 mmHg and 5.6 to 12.6 mmHg, respectively. There was no significant correlation between M and SD in the WHHL rabbit. M and variance (V) of MAP in the WHHL rabbit were significantly higher than those in the normal rabbit. M did not show any significant change with increasing ages, whereas SD increased significantly with aging in the WHHL rabbit. Concentrations of serum total cholesterol and triglyceride in the WHHL rabbit were 475 and 328 mg/dl, which were about nine and seven times as high as those in the normal rabbit, respectively. Macroscopic and histopathological examinations of the aorta revealed development and spread of sclerotic lesions with aging in the WHHL rabbit. We can conclude that development of atherosclerosis with aging in the WHHL rabbit causes malfunction of the baroreceptors, which contributes to hypertension and lability of arterial pressure.

Chemotherapy of depression; use of meprobamate combined with benactyzine (2-diethylaminoethyl benzilate) hydrochloride.

Depression, defined as a state of sadness, with self-reproaches, psychomotor inhibition, sleep disturbance, and impaired appetite, was treated in 35 consecutive patients by the simultaneous use of meprobamate and benactyzine hydrochloride. The meprobamate was given initially in doses of 400 mg. four times daily and, when necessary, gradually increased to 1,200 mg. four times daily; its purpose was to relax and reduce excitability without exerting a significant inhibitory effect. The benactyzine was given initially in doses of 1 mg. four times daily and, when necessary, gradually increased to 3 mg. four times daily; it is a mild anti-depressant particularly effective in relieving the ruminative obsessive aspects of the depressive mood. Close supervision extending over the entire 24-hour span of each day had to be assured because of the risk of suicide. The usual supportive psychotherapy was given concurrently. Three case histories illustrate the procedure. The average duration of treatment was eight weeks, and 20 patients (57%) made a complete and/or social recovery. This is higher than the rate of spontaneous recovery under comparable conditions. It is not as high as the rate of recoveries obtained by electroshock therapy. This treatment is therefore recommended as an initial step in the treatment of depressions, designed to reduce the number of patients requiring electroshock therapy.

Experimental Studies on the Indican Formation. Second Report

In some of the experiments quoted in the previous paper, the indican formation in nephritis was decreased apparently, but the indican in urine and blood was estimated at that time only. Strictly speaking, however, we can not comment on the total amount of produced indican without consideration of the indican in the tissues and organs. Actually, at present we are able to insist that the indican formation increases in nephritis invariably, on the basis of experiments, in which the indican retained in the body has been estimated and added to the indican excreted in reckoning the total amount of produced indican. Here I repeat my proposal: Between the indican formation in an organism and the state of appetite there exists an intimate relation, and when the appetite decreases the amount of indican increases and vice versa. Now I have reached the conclusion that my this proposal is applicable in the case of nephritis as well as in other cases, and it is my belief that the fact that indican increases when the appetite decreases means no more than that indican is produced from body protein.

Experimental Studies on the Indican Formation. First Report

1. Bacterium coli in the intestine and indican in urine never disappear even when the guinea-pigs are nourished only with cabbages. 2. Indican in urine of guinea-pigs increases by only a few hours'fasting. 3. Indican in urine of rabbits does not at all dccrease, rather increases about ten times as much as normal by ten days'fasting. 4. The amount of indican has no conncction with the charaeter of feces. 5. Between the indican formation and the state of appetite there is a very intimate relation; if the appetite decreases, the amount of indican increases, and vice versa, and it may well be said that the decrease of appetite and the increase of indican run quantitatively parallel. 6. The parenteral administration of a large amount of liver or kidney cells has caused the increased excretion of indican. But whether it may be due to the direct action of the constituents of the introduced cells, or to the poor appetite resulting from their administration is questionable. 7. In the early stage of the uran nephritis the total amount of indican in urine and blood is smaller than that of the normal state. But the total amount of indican formed thereby must be larger than that of the normal if we take into consideration the indican retained in the tissues and excrcted vicariously into the digestive tube. 8. The hyperindicanemia in nephritis is the result of increased formation as well as retention of indican. 9. In habu-poison nephritis also the blood contains more indican than normal, and the total amount of indican in urine and blood is larger than that of the normal. 10. The disinfection of the intestinal canal or the rapid discharge of intestinal contents with medicaments does not diminish the amount of indican, but rather increases it. 11. The reaction of urine has no connection with the amount of indican. 12. The parenterally administered sodium oxalate has no influence on the indican formation in guinea-pigs. 13. Except for the indicanemia in renal insufficiency we often meet slight indicancmia in various diseases, which may be regarded as a partial appearence of increased indican, for example, by gastro-intestinal disturbances or inanition. 14. Indican is excreted vicariously from the digestive tube in renal insufficieney. 15. The indicanuria observed clinically in many diseases may be attributed partly to the increased decomposition of body protein due to the poor appctite, and partly to the anomalies of metabolism. 16. Finally I have reached the next conclusion that indican may well be formed also through the metabolic process without the activity of bacteria. In conclusion I wish to express my sincere thanks to Professor Dr. T. Ishikawa for his generous help, criticism and advice throughout the investigation.