Sucrose Sham Feeding Research Articles

Sucrose sham feeding on a binge schedule releases accumbens dopamine repeatedly and eliminates the acetylcholine satiety response

Drinking a sugar solution on an intermittent schedule can promote sugar bingeing and cause signs of dependence while releasing dopamine repeatedly like a drug of abuse. It is hypothesized that sweet taste alone is sufficient for this effect in sucrose bingeing rats. On the theory that acetylcholine in the nucleus accumbens plays a role in satiety, it is further hypothesized that purging the stomach contents will delay acetylcholine release. Rats with gastric fistulas and nucleus accumbens guide shafts for microdialysis were fed 12 h each day. During the first hour, fistulas were open for the sham-feeding group and closed for the real-feeding group, and 10% sucrose was the only food source. For the remaining 11 h, liquid rodent diet was available as well as the 10% sucrose to provide a balanced diet. In microdialysis tests during the first sugar meal on days 1, 2 and 21, extracellular dopamine increased at least 30% each day in both groups. Acetylcholine also increased during the sugar meals for the real-feeding animals, but not during sham feeding. In conclusion, the taste of sugar can increase extracellular dopamine in the nucleus accumbens without fail in animals on a dietary regimen that causes bingeing and sugar dependency. During sham feeding, the acetylcholine satiation signal is eliminated, and the animals drink more. These findings support the hypothesis that dopamine is released repeatedly in response to taste when bingeing on sweet food, and the acetylcholine satiety effect is greatly reduced by purging; this may be relevant to bulimia nervosa in humans.

Altered taste sensitivity in obese, prediabetic OLETF rats lacking CCK-1 receptors

Otsuka Long-Evans Tokushima fatty (OLETF) rats lack the CCK-1 receptor, are hyperphagic, progressively become obese, and develop type-2 diabetes. We recently demonstrated an increased preference for both real and sham feeding of sucrose in this strain, suggesting altered orosensory sensitivity. To investigate taste functions, we used an automated gustometer with 10-s access to different concentrations of various sapid stimuli. Tests were repeated at 10 and 18 wk of age to assess the early and advanced stages of prediabetes, respectively. Compared with age-matched, nonmutant controls, the OLETF rats showed higher avidity for sucrose at both ages. This difference increased as a function of age and tastant concentration. An exaggerated response also occurred for saccharin, alanine, and fructose, but not for Polycose. Similarly, OLETF rats consumed monosodium-glutamate more at the lower concentrations compared with controls, an effect that age also accentuated. In contrast, there was no statistical strain or age differences in responses to NaCl, MgCl2, citric acid, quinine-HCl, and the trigeminal stimulus capsaicin. These findings demonstrate that compared with controls, OLETF rats differ in their gustatory functions with an overall augmented sensitivity for sweet that progresses during prediabetes. This effect explains their overconsumption of sweet solutions and may contribute to the overall hyperphagia and obesity in this strain.

Sucrose sham feeding decreases accumbens norepinephrine in the rat

Noradrenergic projections from the dorsomedial medulla reach the shell of the nucleus accumbens (NAcc), a structure implicated in both reward and feeding behavior. Despite this relationship, the effect of food reward on accumbens norepinephrine (NE) remains uninvestigated. In the course of assessing dopamine (DA) in the NAcc during sucrose ingestion [0.03, 0.1, and 0.3 M; Am. J. Physiol., Regul. Integr. Comp. Physiol., 286 (2004) R31], we also analyzed NE in the microdialysis samples from 14 ad-libitum-fed male rats. In contrast to DA, which increased with sucrose concentration (+20–47%) during sham feeding, in the same animals, NE levels were reduced (approximately −20%), regardless of sucrose concentration. These results demonstrate a novel relationship between accumbens DA and NE during orosensory stimulation with a preferred nutrient.

Oral sucrose stimulation increases accumbens dopamine in the rat.

Although taste can influence meal size and body weight, the neural substrate for these effects remains obscure. Dopamine, particularly in the nucleus accumbens, has been implicated in both natural and nonnatural rewards. To isolate the orosensory effects of taste from possible postingestive consequences, we investigated the quantitative relationship between sham feeding of sucrose and extracellular dopamine in the nucleus accumbens with microdialysis in rats. Sucrose intake linearly increased as a function of concentration (0.03 M, 18.07 +/- 2.41 ml; 0.1 M, 30.92 +/- 2.60 ml; 0.3 M, 43.28 +/- 2.88 ml). Sham feeding also stimulated accumbens dopamine overflow as a function of sucrose solution concentration (0.03 M, 120.76 +/- 2.6%; 0.1 M, 140.28 +/- 7.8%; 0.3 M, 146.27 +/- 5.05%). A second experiment used the same protocol but clamped the amount of sucrose ingested and revealed a similar, concentration-dependent dopamine activation in the nucleus accumbens. This is the first demonstration of a quantitative relationship between the concentration-dependent rewarding effect of orosensory stimulation by sucrose during eating and the overflow of dopamine in the nucleus accumbens. This finding provides new and strong support for accumbens dopamine in the rewarding effect of sucrose.

Behaviorally specific inhibition of sham feeding by amylin

To further characterize amylin’s inhibitory action on feeding, we examined the effects of intraperitoneal injections of amylin on sham feeding of sucrose in food-deprived male rats with chronic gastric cannulas. Thirty and 100 μg/kg amylin reduced sham feeding, but did not terminate it or elicit the behavioral sequence of satiety. Real feeding of sucrose, but not sham feeding, was reduced after injection of 10 μg/kg amylin. Amylin’s inhibitory effect on sham feeding appeared behaviorally specific because neither 30 nor 100 μg/kg amylin affected sham drinking of water in thirsty rats and because no abnormal behaviors occurred. We conclude that amylin has a behaviorally specific satiating effect on sucrose sham feeding that is insufficient to elicit satiety in absence of gastric or postgastric food stimulation.

Capsaicin attenuates feeding suppression but not reinforcement by intestinal nutrients.

During and after a meal, the presence of nutrients in the intestine can be rapidly detected and signaled to the brain via visceral afferents. Intestinal infusions of carbohydrate and fat suppress food intake, and this satiety action is inhibited by capsaicin, a neurotoxin that produces a partial visceral deafferentation. This study determined if the postingestive reinforcing action of nutrients is also suppressed by capsaicin treatment. Food-restricted control and capsaicin-treated rats were trained to drink a flavored solution paired with intraduodenal infusions of carbohydrate (Polycose solution) on some days and, on other days, a differently flavored solution paired with intraduodenal water infusions. In a choice test, both groups displayed a strong preference for the Polycose-paired flavor. In a subsequent satiety test, however, intraduodenal Polycose suppressed sucrose sham feeding in the controls but not in capsaicin-treated rats. The same rats were next trained to associate new flavors with intraduodenal fat (corn oil emulsion) and intraduodenal water infusions. During training, oil infusions reduced oral intakes in the controls much more than in the capsaicin-treated rats. Both groups reliably preferred the oil-paired flavor in the subsequent choice test. These results indicate that, unlike the satiating effect of intestinal carbohydrate and fat, the reinforcing actions of these nutrients are not mediated by capsaicin-sensitive visceral afferents. The data also imply that the postingestive reinforcement produced by nutrients is not dependent on the nutrients' satiating quality.

Persistence of sham feeding after intragastric meals in the rat: Concentration-intake relations

In rats sham fed through esophageal fistulas, responsiveness to sucrose over a range of concentrations was assessed under two conditions: immediately following a large intragastric (IG) preload of liquid diet, and after 10 h of deprivation with no preload. The preload had no reliable effect on sucrose sham feeding at any sucrose concentration. Therefore, the insensitivity of sham feeding to IG loads is not confined to intense or highly palatable oral stimuli, but extends even to minimally effective ones.

Raclopride microinjected into the nucleus accumbens inhibits sucrose sham feeding

Raclopride microinjected into the nucleus accumbens inhibits sucrose sham feeding

(—) threo-chlorocitric acid decreases sham feeding of sucrose in rats

The contribution of changes in rate of gastric emptying to the anorectic effect of (-)- threo-chlorocitric acid (chlorocitrate) was assessed by examining the effect of this drug in sham feeding rats, a preparation where gastric distention does not occur. Gavage administration of chlorocitrate (100–400 mg·kg −1) decreased sham and real feeding of 20% sucrose in a dose-related manner. In sham-feeding rats, the minimal effective dose was 200 mg·kg −1. The anorectic effect was evident at 60 min after 200 mg·kg −1 and 30 min after 400 mg·kg −1 . In real-feeding rats, the minimal effective dose was 100 mg·kg −1 and for all doses tested the effect was apparent at the 15-min time point. In a second experiment, the effect of chlorocitrate (100–400 mg·kg −1) on gastric emptying of 20% sucrose was examined. Chlorocitrate (200 and 400 mg·kg −1) had a modest but significant inhibitory effect on gastric emptying; however, the effect was not dose-related. Inasmuch as chlorocitrate decreased sham feeding, its anorectic effect cannot be solely attributed to inhibition of gastric emptying. However, because chlorocitrate was more potent in the real-feeding condition relative to sham feeding, and the time course of the response in the two feeding conditions was different, part of chlorocitrate's anorectic effect may depend on postingestive cues such as gastric distention.

Infra-additivity of combined treatments with selective D 1 and D 2 receptor antagonists for inhibiting sucrose reinforcement

Selective antagonists of either the D 1 receptor (SCH 23390) or of the D 2 receptor (raclopride) produce a dose-related inhibition of sucrose sham feeding in the rat. We investigated the effect of combined treatments with these antagonists on sucrose sham feeding and observed infra-additivity of inhibition across a range of doses. On the basis of this observed occlusive relationship, we conclude that the relevant D 1 and D 2 receptor mechanisms mediating sweet taste reward do not function independently.

Similar effect of raclopride and reduced sucrose concentration on the microstructure of sucrose sham feeding

Raclopride, a dopamine D 2 antagonist, decreases the intake of sucrose solutions during sham feeding tests and of water during sham drinking tests in rats. To determine whether the reduced intake of sucrose by raclopride was due to a decrease in the positive reinforcing effect of sucrose or to an impairment in licking movements, we compared the rate, efficiency and pattern of licking after two procedures each of which decreased sucrose sham intake about 50%; these were (a) pretreatment with raclopride (ID 50), and (b) dilution of the sucrose concentration sham fed from 10 to 5%. Microstructural analysis failed to reveal significant differences in the rate, efficiency (licks/ml) or patterns of licking between these two procedures. When raclopride inhibited the sham drinking of water, the rate and efficiency of licking were normal, but the patterns of licking were qualitatively different from those observed when raclopride inhibited the sham feeding of sucrose. We conclude that raclopride decreases intake of 10% sucrose during sham feeding and intake of water during sham drinking by decreasing the positive reinforcing potency of the orosensory effect(s) of the two liquids on licking rather than by decreasing the ability to lick. These results provide strong evidence that interaction of dopamine at D 2 receptors is necessary for the normal sensory and/or hedonic processing of the orosensory stimuli produced by sucrose during sham feeding and by water during sham drinking.

Enhanced anorectic potency of naloxone in rats sham feeding 30% sucrose: Reversal by repeated naloxone administration

The time-course of naloxone-anorexia was monitored in gastric-fistulated rats sham feeding sucrose (10%, 20%, 30%) solutions. Naloxone reduced sham intake dose dependently without affecting feeding initiation and in a manner which resembled the effects of progressive sucrose dilution. However, when rats sham fed 30% sucrose there was a 2-fold increase in the anorectic potency of naloxone. This exaggerated response was prevented by prior repeated naloxone treatment (5 mg/kg IP, bi-daily), concurrent with the stabilization of sham intake levels (4 days). A further experiment ruled out the possibility that tolerance develops to naloxone effects on this treatment schedule, since intact rats showed a suppression of wet mash consumption following repeated naloxone treatment which was equivalent to an acute naloxone challenge. It is proposed that 1) repeated sucrose sham feeding enhances opioid release and leads to opioid receptor adaptation (down-regulation); 2) repeated (chronic) naloxone treatments have an opposite effect on opioid receptors (up-regulation); 3) the two manipulations, in combination, counteract each other's effects. These behavioural data demonstrate dynamic changes in sham-feeding performance as a function of sucrose concentration and naloxone treatments, reinforce the importance of palatability in naloxone-anorexia, and support opioid involvement in orosensory reward.

Effects of 5-hydroxytryptamine and [formula omitted] on sham feeding and sham drinking in the gastric-fistulated rat

Previous experiments indicated that drug treatments which increase serotonergic activity produce dose-related reductions in sucrose sham feeding. In the present studies, 5-hydroxytryptamine (5-HT, 2 mg/kg, IP) significantly reduced sham feeding; its effect was reversed by the peripheral 5-HT receptor antagonist, xylamidine (3 mg/kg, IP). At the same dose, 5-HT did not affect water sham drinking. These are the first data to implicate serotonergic activity at peripherally located 5-HT receptors in the modulation of sucrose sham feeding. d- Fenfluramine (3 mg/kg, IP) also reduced sham feeding, an effect that was weakly attenuated by xylamidine, suggesting substantial mediation of its effect by centrally located 5-HT receptors. Sham drinking was reduced by d- fenfluramine (3 mg/kg), although to a lesser degree. In comparison with the previous studies, the present data suggest that in smaller doses d- fenfluramine is relatively selective in its effect on sham feeding, but that, in larger doses, the selectivity may be lost.

Central and Peripheral 5‐HT Receptors Mediate Reductions in Sucrose Sham Feeding in the Rat

Central and Peripheral 5‐HT Receptors Mediate Reductions in Sucrose Sham Feeding in the Rat

Failure to detect increases in brain dopamine turnover in corn oil and sucrose sham feeding rats

Failure to detect increases in brain dopamine turnover in corn oil and sucrose sham feeding rats

Microstructural analysis of the inhibition of sucrose sham feeding by SCH 23390

Microstructural analysis of the inhibition of sucrose sham feeding by SCH 23390

Relationships between mesolimbic dopamine function and eating behavior.

These experiments are the first to correlate a specific stimulus of eating--the orosensory stimulation by sucrose--to mesolimbic dopaminergic activity. The pharmacological results and the increase in hypothalamic DOPAC/DA are convergent evidence for this relationship. The meaning of the relationship is not clear. The possibility that the decreased intake after dopaminergic receptor antagonist treatment and the increase in hypothalamic DOPAC/DA is related to the ingestive movements necessary for sham feeding seems unlikely for the following reasons: first, at least one dose of the antagonist had a preferential inhibition on sucrose intake compared to water intake; second, the D1 and D2 selective receptor antagonists decreased the initial rate of sucrose intake, but did not affect the rate of decay of sucrose intake over a 30-min test; third, in the second neurochemical experiment (Table 1), the volume ingested during 9 min of sham feeding 10% sucrose was not significantly different from the volume ingested from sham feeding 40% sucrose, but there was a significantly larger increase in the hypothalamic DOPAC/DA after 40% sucrose. Of course, a finer measurement of movements, such as lick rate, may reveal a significant difference that would correlate with the metabolic change. Fourth, striatal DOPAC/DA did not change during sham feeding of sucrose. Fifth, Bailey et al. demonstrated that a response-frequency summation analysis of the inhibitory effect of pimozide on sucrose intake did not reveal a motoric deficit. Thus, we interpret the increase of hypothalamic DOPAC/DA during the sham feeding of sucrose as evidence that activation of mesolimbic dopaminergic terminals in the hypothalamus is necessary for the normal processing of the central sensory and/or positive-reinforcing information produced by oral sucrose stimulation. Experiments are in progress to test this hypothesis and to attempt to distinguish between the sensory and positive-reinforcing effects of sucrose during sham feeding. In addition to generating this specific hypothesis concerning sucrose and hypothalamic DA activity, the results of these experiments suggest that the sham feeding preparation will be useful for the analysis of the important problem of the natural reinforcing properties of sweet taste. And finally, since sham feeding of sucrose is a form of oral self-stimulation, it provides a new experimental tool for comparing the role of central DA mechanisms in the positive-reinforcing effects of food, psychostimulant self-administration, and intracranial electrical self-stimulation.

Comparison of the Effects of Selective D1 and D2 Receptor Antagonists on Sucrose Sham Feeding and Water Sham Drinkinga

Annals of the New York Academy of SciencesVolume 537, Issue 1 p. 534-537 Comparison of the Effects of Selective D1 and D2 Receptor Antagonists on Sucrose Sham Feeding and Water Sham Drinkinga L. H. SCHNEIDER, Corresponding Author L. H. SCHNEIDER New York Hospital-Cornell Medical Center, White Plains, New York 10605To whom correspondence should be addressed.Search for more papers by this authorD. GREENBERG, D. GREENBERG New York Hospital-Cornell Medical Center, White Plains, New York 10605Search for more papers by this authorG. P. SMITH, G. P. SMITH New York Hospital-Cornell Medical Center, White Plains, New York 10605Search for more papers by this author L. H. SCHNEIDER, Corresponding Author L. H. SCHNEIDER New York Hospital-Cornell Medical Center, White Plains, New York 10605To whom correspondence should be addressed.Search for more papers by this authorD. GREENBERG, D. GREENBERG New York Hospital-Cornell Medical Center, White Plains, New York 10605Search for more papers by this authorG. P. SMITH, G. P. SMITH New York Hospital-Cornell Medical Center, White Plains, New York 10605Search for more papers by this author First published: October 1988 https://doi.org/10.1111/j.1749-6632.1988.tb42151.xCitations: 10 a The work of one of the authors (L. H. C.) was supported by Grant MH90400, and the work of another of the authors (G. P. S.) was supported by Grant MH15455. AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Citing Literature Volume537, Issue1The Mesocorticolimbic Dopamine SystemOctober 1988Pages 534-537 RelatedInformation

A comparison of the effects of atropine on real-feeding and sham-feeding of sucrose in rats

In Experiment 1 the influence of atropine methyl nitrate on the sham-feeding response of adult female rats to sucrose solution was determined. Atropine (1 or 5 mg/kg) reliability suppressed the sham-intake of sucrose when the drug was administered 30 or 0 min prior to, or 17 min after the start of the feeding session. The suppressive effect was less, however, when the drug was administered 30 min before testing compared to the other two injection-test conditions. In Experiment 2 atropine failed to reliably decrease the real-feeding of a sucrose solution whether it was injected 30, 15, or 0 min prior to testing. These results were replicated in Experiment 3; atropine (0 min injection-test interval) reduced the sham-intake but not the real-intake of a sucrose solution. However, atropine decreased the rate of feeding under both real- and sham-feeding conditions. The fact that atropine reduced feeding rate but not meal size in the real-feeding condition was attributed to the drug's lack of effect on postingestive satiety. The present findings along with other recent results indicate that (1) the injection-test interval is a potentially important variable in studies involving atropine; (2) results obtained with sham-feeding animals do not always generalize to real-feeding animals; and (3) cholinergically-mediated cephalic responses are of questionable importance in the control of meal size.

Sham feeding of sucrose increases the ratio of 3,4-dihydroxyphenylacetic acid to dopamine in the hypothalamus

Recent pharmacological experiments suggested that central dopaminergic (DA) mechanisms are necessary for the normal eating response to sweet stimuli. To test this hypothesis, we measured the ratio of dihydroxyphenylacetic acid (DOPAC) to dopamine (DA) in forebrain DA terminal fields during the sham feeding of sucrose (1–40%) by rats after 17 hr of food deprivation. After 9 min of sham feeding 10% or 40% sucrose, DOPAC/DA increased in the hypothalamus, but not in other forebrain regions including the n. accumbens, amygdala, and pyriform cortex. This increase in hypothalamic DOPAC/DA did not occur after 9 min of sham feeding 1%, 1.25%, or 2.5% sucros. The increased DA metabolism required that sham feeding of 10% or 40% sucrose be maintained for longer than 3 min, because no increase of DOPAC/DA was observed in any forebrain region after 3 min of sham feeding. These results are strong evidence that hypothalamic DA mechanisms are activated by the sham feeding of sucrose solutions and they support the hypothesis that central DA mechanisms are necessary for the normal eating response to sweet stimuli.