Negative anticipatory contrast: does it involve anticipation of an impending reward?

Negative anticipatory contrast (NAC) corresponds to the suppression in consumption of a first rewarding substance (e.g., saccharin 0.15%) when it is followed daily by a second preferred substance (e.g., sucrose 32%). The NAC has been interpreted as resulting from anticipation of the impending preferred reward and its comparison with the currently available first reward [Flaherty, C.F., Rowan, G.A., 1985. Anticipatory contrast: within-subjects analysis. Anim. Learn. Behav. 13, 2-5]. In this context, one should expect that devaluation of the preferred substance after the establishment of the NAC would either reduce or abolish the contrast effect. However, contrary to this prediction, the results of the present study show that the NAC is insensitive to devaluation of the second, preferred, substance. This allows one to question that interpretation. The results reported in this study support the view that the NAC effect is controlled by memory of the relative value of the first solution, which is updated daily by means of both a gustatory and/or post-ingestive comparison of the first and second solutions, and memory of past pairings.     

Expression of Fos during sham sucrose intake in rats with central gustatory lesions

For humans and rodents, ingesting sucrose is rewarding. This experiment tested the prediction that the neural activity produced by sapid sucrose reaches reward systems via projections from the pons through the limbic system. Gastric cannulas drained ingested fluid before absorption. For 10 days, the rats alternated an hour of this sham ingestion between sucrose and water. On the final test day, half of them sham drank water and the other half 0.6 M sucrose. Thirty minutes later, the rats were killed and their brains immunohistochemically stained for Fos. The groups consisted of controls and rats with excitotoxic lesions in the gustatory thalamus (TTA), the medial (gustatory) parabrachial nucleus (PBN), or the lateral (visceral afferent) parabrachial nucleus. In controls, compared with water, sham ingesting sucrose produced significantly more Fos-positive neurons in the nucleus of the solitary tract, PBN, TTA, and gustatory cortex (GC). In the ventral forebrain, sucrose sham licking increased Fos in the bed nucleus of the stria terminalis, central nucleus of amygdala, and the shell of nucleus accumbens. Thalamic lesions blocked the sucrose effect in GC but not in the ventral forebrain. After lateral PBN lesions, the Fos distributions produced by distilled H(2)O or sucrose intake did not differ from controls. Bilateral medial PBN damage, however, eliminated the sucrose-induced Fos increase not only in the TTA and GC but also in the ventral forebrain. Thus ventral forebrain areas associated with affective responses appear to be activated directly by PBN gustatory neurons rather than via the thalamocortical taste system.     

Sugar Overconsumption during Adolescence Selectively Alters Motivation and Reward Function in Adult Rats

Background

There has been a dramatic escalation in sugar intake in the last few decades, most strikingly observed in the adolescent population. Sugar overconsumption has been associated with several adverse health consequences, including obesity and diabetes. Very little is known, however, about the impact of sugar overconsumption on mental health in general, and on reward-related behavioral disorders in particular. This study examined in rats the effects of unlimited access to sucrose during adolescence on the motivation for natural and pharmacological rewards in adulthood.

Methodology/Principal Findings

Adolescent rats had free access to 5% sucrose or water from postnatal day 30 to 46. The control group had access to water only. In adulthood, rats were tested for self-administration of saccharin (sweet), maltodextrin (non-sweet), and cocaine (a potent drug of abuse) using fixed- and progressive-ratio schedules, and a concentration-response curve for each substance. Adult rats, exposed or not exposed to sucrose, were tested for saccharin self-administration later in life to verify the specificity of adolescence for the sugar effects. Sugar overconsumption during adolescence, but not during adulthood, reduced the subsequent motivation for saccharin and maltodextrin, but not cocaine. This selective decrease in motivation is more likely due to changes in brain reward processing than changes in gustatory perception.

Conclusions/Significance

Sugar overconsumption induces a developmental stage-specific chronic depression in reward processing that may contribute to an increase in the vulnerability to reward-related psychiatric disorders.     

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.     

Sham feeding corn oil increases accumbens dopamine in the rat

Both real and sham feeding of sucrose increase dopamine (DA) overflow in the nucleus accumbens (NAc). Fat is another constituent of foods that is inherently preferred by humans and rodents. We examined the affect of sham feeding corn oil in rats that were food and water deprived overnight. Rats were implanted with guide cannulas aimed at the NAc, as well as gastric fistulas. On alternate days, they were trained to sham lick 100% corn oil or distilled water (dH2O) for 20 min in the morning. Twenty-minute microdialysis samples were taken before, during, and after sham licking. DA and monoamines were analyzed by reverse-phase HPLC with coulometric detection. The results show that DA release in the NAc was significantly increased during sham licking of corn oil compared with the prior baseline (157.5+/-18.8%, n=12). During sham licking of dH2O, DA release in the NAc was not changed (93.0+/-4.0%, n=15). This experiment demonstrates that sham feeding of corn oil releases accumbens DA in a manner similar to ingestion of sucrose. Although both stimuli may have an olfactory component, sucrose is a gustatory, and 100% corn oil appears to be a trigeminal stimulus. Thus these data support the hypothesis that different sensory modalities produce reward using the same or closely related substrates in the forebrain.     

Effects of melanin-concentrating hormone on licking microstructure and brief-access taste responses

The effects of intracerebroventricular application of melanin-concentrating hormone (MCH) on licking for sucrose, quinine hydrochloride (QHCl), and water solutions were evaluated in two experiments. In experiment 1, rats received 90-min access to sucrose and water solutions after MCH or vehicle microinjection to the third ventricle (3V). MCH increased intake largely through increases in the rate of licking early in the meal and in the mean duration of lick bursts, suggesting an effect on gustatory evaluation. Therefore, in experiment 2, brief access tests were used with a series of sucrose and QHCl concentrations to behaviorally isolate the effects of intracerebroventricular MCH on gustatory evaluation. MCH uniformly increased licking for all sucrose solutions, water, and weak concentrations of QHCl; however, it had no effect on licking for the strongest concentrations of QHCl, which were generally avoided under control conditions. Thus MCH did not produce nonspecific increases in oromotor activity, nor did it change the perceived intensity of the tastants. We conclude that MCH enhanced the gain of responses to normally accepted stimuli at a phase of processing after initial gustatory detection and after the decision to accept or reject the taste stimulus. A comparison of 3V NPY and MCH effects on licking microstructure indicated that these two peptides increased intake via dichotomous behavioral processes; although NPY suppressed measures associated with inhibitory feedback from the gut, MCH appeared instead to enhance measures associated with hedonic taste evaluation.     

Reinforcer satiation and resistance to change of responding maintained by qualitatively different reinforcers

In previous research on resistance to change, differential disruption of operant behavior by satiation has been used to assess the relative strength of responding maintained by different rates or magnitudes of the same reinforcer in different stimulus contexts. The present experiment examined resistance to disruption by satiation of one reinforcer type when qualitatively different reinforcers were arranged in different contexts. Rats earned either food pellets or a 15% sucrose solution on variable-interval 60-s schedules of reinforcement in the two components of a multiple schedule. Resistance to satiation was assessed by providing free access either to food pellets or the sucrose solution prior to or during sessions. Responding systematically decreased more relative to baseline in the component associated with the satiated reinforcer. These findings suggest that when qualitatively different reinforcers maintain responding, relative resistance to change depends upon the relations between reinforcers and disrupter types.     

Central gustatory projections and side-specificity of operant antennal muscle conditioning in the honeybee

Gustatory stimuli to the antennae, especially sucrose, are important for bees and are employed in learning paradigms as unconditioned stimulus. The present study identified primary antennal gustatory projections in the bee brain and determined the impact of stimulation of the antennal tip on antennal muscle activity and its plasticity. Central projections of antennal taste hairs contained axons of two morphologies projecting into the dorsal lobe, which is also the antennal motor centre. Putative mechanosensory axons arborised in a dorso-lateral area. Putative gustatory axons projected to a ventro-medial area. Bees scan gustatory and mechanical stimuli with their antennae using variable strategies but sensory input to the motor system has not been investigated in detail. Mechanical, gustatory, and electrical stimulation of the ipsilateral antennal tip were found to evoke short-latency responses in an antennal muscle, the fast flagellum flexor. Contralateral gustatory stimulation induced smaller responses with longer latency. The activity of the fast flagellum flexor was conditioned operantly by pairing high muscle activity with ipsilateral antennal sucrose stimulation. A proboscis reward was unnecessary for learning. With contralateral antennal sucrose stimulation, conditioning was unsuccessful. Thus, muscle activity induced by gustatory stimulation was important for learning success and conditioning was side-specific.     

A moment-by-moment comparsion of sucrose and saccharin drinking by the rat

Comparisons were made between the ingestion patterns in ratsto a 0.2% sodium saccharin solution and to a 32% sucrose solutionin both short-term (30 min, one solution only) and long-term(23 h, solution versus water) tests. The resolution of measurementin the short- and long-term tests was 0.5 and 30 s respectively.Analysis programs for both procedures allowed for a quantificationof the ingestion patterns over time, showing details of thelick bursts in the short-term tests and ingestion bouts in the23-h tests. Although the quantities of sucrose and saccharinconsumed in the long-term tests were equal, the drinking patternsfor water, saccharin and sucrose were markedly different duringthe three testing periods, (i) There were fewer drinking boutsto the sucrose than to the saccharin or water, (ii) The averagebout of sucrose was much larger than the saccharin or waterbouts, (iii) The inter-bout intervals for sucrose were muchlonger than those for saccharin, (iv) Nearly half of the sucroseintake occurred during the ‘lights-on’ portion ofthe 23-h drinking period as compared to less than one-thirdfor saccharin or water, (v) Food intake when saccharin was presentwas equal to normal food intake when only water was available.However, in the presence of sucrose, the number and the sizeof feeding bouts decreased resulting in a 36% reduction in foodintake. Similar results were found in the short-term tests whencomparing sucrose and saccharin ingestion in that the quantitiesconsumed were not reliably different, but the ingestion patternswere, (i) The rats had many more bursts of licking saccharinthan sucrose, (ii) The saccharin bursts were much shorter thanthose for sucrose, (iii) Saccharin licking occurred off andon throughout the 30-min testing period while sucrose was consumedat a rapid rate at first and then terminated in 10–15min from the period onset. Inferences about the different tastesof saccharin and sucrose to the rat arc drawn from the detailedpattern analyses.     

Rapid calorie metering inad lib rats

Adult wistar rats of either sex housed in individual cages and fedad lib were used to investigate the effects of calorie content and taste on ingestion. A 15 min single-choice solution (water, quinine, sucrose, saccharin) test as well as 1 h mixed diet (stock diet, sucrose-mixed, saccharin-mixed, quinine-mixed) tests were used. Calorically-rich sucrose either in solution or in mixed-diet was preferentially ingested. Tasteper se has not influenced calorie intake, as intake on sweet saccharin (3.4 ±0.4 cal) or on bitter quinine (3.3 ±0.6 cal) was similar to intake on stock diet (4.8 ±0.8 cal). Increased 5 min intake on sucrose solution (4.6 ±0.1 ml) over intake of other test solutions (saccharin 3.5 ±0.2 ml, quinine, 1.2 ±0.3 ml, water 2.1 ±0.1 ml) and calorie intake suppression on 1 h stock diet immediately following sucrose solution intake, indicate rapid calorie metering, probably based on fast-acting specific gustatory signals     

Female rats show a bimodal preference response to the artificial sweetener sucralose

The preference of female Sprague-Dawley rats for sucralose, a non-nutritive sweetener derived from sucrose, was evaluated in 23 h two-bottle tests with water or saccharin. Overall, the rats displayed weak or no preferences for sucralose (0.25-4 g/l) over water but strong preferences for saccharin (0.5-8 g/l) over water and saccharin (1 g/l) over sucralose (0.5 g/l). The rats also preferred a saccharin + sucrose mixture to sucrose, but sucrose to a sucralose + sucrose mixture. There were marked individual differences in sucralose preferences: about half the rats preferred sucralose to water at some concentrations while most remaining rats avoided sucralose. Both subgroups preferred saccharin to sucralose. Sucralose appears to have an aversive off-taste that reduces its palatability to rats.     

Preference for sucralose predicts behavioral responses to sweet and bittersweet tastants

Rats can be classified as either sucralose avoiders (SA) or sucralose preferrers (SP) based on their behavioral responses in 2-bottle preference, 1-bottle intake, and brief-access licking tests. The present study demonstrates that this robust phenotypic variation in the preference for sucralose predicts acceptance of saccharin, an artificial sweetener with a purported concentration-dependent "bitter" side taste and a 0.25 M sucrose solution adulterated with increasing concentrations of quinine hydrochloride (QHCl). Specifically, SA displayed decreased preference for and intakes of saccharin (≥41.5 mM) and sucrose-QHCl (>0.5 mM QHCl) solutions, relative to SP. In a second experiment involving brief-access (30-s) tests, SP and SA did not differ in their unconditioned licking responses across a range of sodium chloride or QHCl solutions (0.03-1 mM). However, the acceptability threshold for sucrose was lower in SA, relative to SP (0.06 and 0.13 M, respectively). Our findings suggest that phenotypic differences in sucralose preference are indicative of a more general difference in the hedonic processing of stimuli containing "bittersweet" or "sweet" taste qualities.     

Retention of taste quality following brief exposure to sucrose

Rats were given either 32% sucrose or 4% sucrose during preshiftand 4% sucrose postshift. The preshift and postshift sessionseach consisted of single five minute access periods to the sucrosesolutions. Measures of lick-rate showed that the shifted ratslicked less of the 4% sucrose than the unshifted rats, a negativecontrast effect, and that this negative contrast effect occurredwith intervals ranging from 1 hr to 70 hrs separating the briefpreshift and postshift exposure periods. The results were discussedin terms of the duration of gustatory memories, particularlyin reference to the conditioned aversion literature and somerunway contrast phenomena.     

'Thermal taste' predicts higher responsiveness to chemical taste and flavor

Individual differences in taste perception have been explained in part by variations in peripheral innervation associated with the genetic ability to taste the bitter substances PTC and PROP. In the present study we report evidence of another source of individual differences that is independent of taste stimulus, taste quality, or gustatory nerve. Individuals who perceived taste from thermal stimulation alone (thermal taste) gave significantly higher taste ratings to chemical stimuli--often by a factor of >2:1--than did individuals who perceived no taste from thermal stimulation. This was true for all taste stimuli tested (sucrose, saccharin, sodium chloride, citric acid, quinine sulfate, MSG and PROP), for all three gustatory areas of the mouth (anterior tongue, posterior tongue and soft palate) and for whole-mouth stimulation. Moreover, the same individuals reported stronger sensations from the olfactory stimulus vanillin, particularly when it was sensed retronasally. The generality of the thermal-taster advantage and its extension to an olfactory stimulus suggests that it arises from individual differences in CNS processes that are involved in perception of both taste and flavor.     

Memory for Brief, Widely Spaced Odor Presentations in the Rat

Rats trained on a series of 16 novel 2-odor discrimination tasksusing a 10-s intertrial interval (ITI) rapidly improved in performanceand made only 0—3 errors by the end of the test series.They were then tested on other novel pairs of odors, but witha 10- and a 30-min interval between trials. There was no decrementin performance accuracy in the longer ITI tests and, in mostcases, criterion performance was achieved after making zeroor 1 error after the first (information) trial. These resultsdemonstrate that rats have the capacity to remember for at least30 min whether a single brief presentation of a novel odor wasfollowed by a reward.     

Generalization of learned taste aversions in rabbits: similarities among gustatory stimuli

Although rabbits have been used in a number of electrophysiologicaland anatomical studies on the gustatory system, there have beenfew behavioral experiments on these animals and these have beenlimited to studies of taste preference. The similarities amonga number of gustatory stimuli were assessed in rabbits by measuringthe generalization patterns in a conditioned taste aversionexperiment. Rabbits were trained to take their daily rationof water within a 30-min session, during which the number oflicks per 10-s presentation of a drinking tube could be recorded.During one of these sessions, one of 12 stimuli (sucrose, fructose,Na-saccharin, NaCI, NaNO₃, Na₂SO₄, KC1, NH₄C1, CaCl₂, HC1, QHC1or urea) was presented, followed by i.p. injection of LiCl toproduce a conditioned taste aversion. Animals were then testedwith all of the stimuli and the amount of suppression of lickingwas used as a measure of stimulus generalization. The patternsof generalization were compared for the test and conditioningstimuli separately. Some nonreciprocities were seen betweenthe conditioning and test stimuli, which reflected the occurrenceof multiple taste qualities and the tendency for aversions togeneralize more to stronger stimuli than to weaker ones. Principalcomponents analysis of the stimulus relationships showed thatrabbits responded to these stimuli in a fashion similar to thatof other mammals, including humans. Within the principal componentssolution, there were strong similarities among the sugars, thesodium salts, the nonsodium salts and the bitter-tasting stimuli.     

Behavioral consequences of exposure to a high fat diet during the post-weaning period in rats

We explored the impact of exposure to an obesogenic diet (High Fat–High Sucrose; HFS) during the post-weaning period on sweet preference and behaviors linked to reward and anxiety. All rats were fed chow. In addition a HFS-transient group had access to this diet for 10 days from post-natal (PN) day 22 and a HFS-continuous group continued access until adult. Behavioral tests were conducted immediately after PN 32 (adolescence) or after PN 60 (adult) and included: the condition place preference (CPP) test for chocolate, sugar and saccharin preference (anhedonia), the elevated plus maze (anxiety-like behavior) and the locomotor response to quinpirole in the open field. Behavior was unaltered in adult rats in the HFS-transient group, suggesting that a short exposure to this obesogenic food does not induce long-term effects in food preferences, reward perception and value of palatable food, anxiety or locomotor activity. Nevertheless, rats that continued to have access to HFS ate less chocolate during CPP training and consumed less saccharin and sucrose when tested in adolescence, effects that were attenuated when these rats became adult. Moreover, behavioral effects linked to transient HFS exposure in adolescence were not sustained if the rats did not remain on that diet until adult. Collectively our data demonstrate that exposure to fat and sucrose in adolescence can induce immediate reward hypofunction after only 10 days on the diet. Moreover, this effect is attenuated when the diet is extended until the adult period, and completely reversed when the HFS diet is removed.     

Quantitative trait loci associated with short-term intake of sucrose, saccharin and quinine solutions in laboratory mice.

The goal of this study was simultaneously to map two genetic loci which, collectively, have a large effect on intake of sucrose, saccharin and quinine solutions in mice. These loci had been previously identified using long-term measurements with the traditional two-bottle test, but the present study used a short-term, one-bottle test. Intake of distilled water, 100 mM sucrose, 10 mM sodium saccharin and 1.1 mM quinine HCl over 6 h was measured on two occasions from a non-deprived group of 61 male and 72 female F2 mice derived from a cross of the C57BL/6J and DBA/2J mouse strains and used to detect quantitative trait loci (QTL). DNA from each animal was typed for polymorphisms in anonymous microsatellite markers on mouse chromosomes 4 and 6. Saccharin and sucrose relevant QTL were detected on distal chromosome 4 and a quinine relevant QTL was detected on medial/distal chromosome 6 in the region of Prp. The location of these QTL and the proportion of phenotypic variance they accounted for were similar to those arrived at following previous determinations using the two-bottle test. Measurement stability for the three gustatory phenotypes was high, product-moment correlation coefficients between first and second determinations varying between approximately 0.80 for sucrose and saccharin and 0.73 for quinine. QTL parameters assessed independently for first and second presentations of sucrose and saccharin were stable, but the location of the quinine QTL differed between presentations. The present experiment illustrates the utility of a 6 h fluid intake test in the mapping of Sac and Qui loci. The short duration of the test provides a simple means of measuring variation in gustatory processes and the discovery that these loci influence short-term as well as long-term fluid intake extends understanding of the mechanism of gene action.     

Melanocortin-4 receptor-null mice display normal affective licking responses to prototypical taste stimuli in a brief-access test

We tested whether MC4R null mice display altered gustatory function relative to wild-type controls that may contribute to the characteristic hyperphagia and obesity associated with this gene deletion. Mice were tested for their licking responses to prototypical taste solutions (sucrose, NaCl, quinine, citric acid) in series of daily 30-min sessions in which a range of concentrations of each tastant was available in randomized blocks of 5-s trials. Notwithstanding some minor deviations, the concentration-response functions of the MC4R null and wild-type mice were basically the same for all of the prototypical compounds tested here. Thus, taste-based appetitive and avoidance behavior is expressed in the absence of the MC4 receptor, demonstrating that this critical component in the melanocortin system is not required for normal affective gustatory function to be maintained.     

Classical reward conditioning in Drosophila melanogaster

Negatively reinforced olfactory conditioning has been widely employed to identify learning and memory genes, signal transduction pathways and neural circuitry in Drosophila. To delineate the molecular and cellular processes underlying reward-mediated learning and memory, we developed a novel assay system for positively reinforced olfactory conditioning. In this assay, flies were involuntarily exposed to the appetitive unconditioned stimulus sucrose along with a conditioned stimulus odour during training and their preference for the odour previously associated with sucrose was measured to assess learning and memory capacities. After one training session, wild-type Canton S flies displayed reliable performance, which was enhanced after two training cycles with 1-min or 15-min inter-training intervals. Higher performance scores were also obtained with increasing sucrose concentration. Memory in Canton S flies decayed slowly when measured at 30 min, 1 h and 3 h after training; whereas, it had declined significantly at 6 h and 12 h post-training. When learning mutant t beta h flies, which are deficient in octopamine, were challenged, they exhibited poor performance, validating the utility of this assay. As the Drosophila model offers vast genetic and transgenic resources, the new appetitive conditioning described here provides a useful tool with which to elucidate the molecular and cellular underpinnings of reward learning and memory. Similar to negatively reinforced conditioning, this reward conditioning represents classical olfactory conditioning. Thus, comparative analyses of learning and memory mutants in two assays may help identify the molecular and cellular components that are specific to the unconditioned stimulus information used in conditioning.