Conditioned changes in appetitive and consummatory responses to flavors paired with oral or nutrient reinforcement among adult rats

Recent studies of the behavioral organization of conditioned flavor preferences have suggested the involvement of at least two separate learning systems-an appetitive response system sensitive to the oral hedonic properties of the reinforcer, and a consummatory response system sensitive to its nutrient properties. However, these prior studies were conducted with weanling rats, that differ from adults in terms of their prior experience with food, their learning competencies, and the peculiar ontogenetic constraints on their behavior. It is, therefore, unknown whether flavor preference behaviors are similarly organized in adult rats. In this experiment, adult rats were trained to associate a specific CS flavor with either the sweet taste or the postingestive nutrient effects of sucrose. Conditioned appetitive orienting and consummatory oral responding to the CS flavors were then measured. Unlike weanling rats, adult rats exhibited both conditioned appetitive behavior and conditioned consummatory behavior in response a CS that was previously paired with either oral hedonic or nutrient reinforcement. These results suggest a set of important developmental changes in the neurobehavioral mechanisms of flavor preference learning in the postweaning period.     

Modulation of behavioral and insulin responses by contextual stimuli paired with food

A context-like conditioned stimulus (CS) previously paired with a food unconditioned stimulus (US) enhanced both food-related activity and insulin secretion in rats. Experiment 1 documented the effectiveness of an appetitive conditioning procedure in which a 10 sec visual CS ("x") was followed by food when embedded within one 35 sec auditory CS ("A"), but not another ("B"). Approach to a food magazine during x was enhanced (facilitated) when x was within A, as compared to within B or alone. Experiment 2 documented the adequacy of blood sampling and insulin assay procedures that could be accommodated to the conditioning procedure. Plasma insulin was observably different after unconditioned deliveries of glucose solutions of different intensities. In Experiment 3, training as in Experiment 1 was followed by testing for food magazine approach and changes in insulin levels following x alone or in the presence of A or B. It was demonstrated that the A cue enhanced both responses. The results support the view [e.g., (18,19)] that insulin secretion is in part under the control of environmental cues, and findings (22) that show that conditioned context-like cues can modulate consummatory responding to punctate CSs.     

Conditioned flavor preference learning by intragastric administration of l-glutamate in rats

The preference for foods or fluids in rats is partly dependent on its postingestive consequences. Many studies have investigated postingestive effect of high caloric substances, such as carbohydrate or fat. In this study, we examined postingestive effect of l-glutamate at the preferable concentration using conditioned flavor preference paradigm. Adult male rats with chronic intragastric (IG) cannula were trained to drink a flavored solution (conditioned stimulus; CS+) paired with IG infusion of nutrient solution and another flavored solution (CS−) with IG distilled water infusion on alternate days. The nutrient solution was 60 mM monosodium l-glutamate, sodium chloride or glucose. Before and after conditioning, rats received 30 min two-bottle choice tests for CS+ and CS− solution. All groups exhibited no significant preference for CS+ in pre-test period. By the last half of conditioning period, intake of CS+ solution was significantly higher than that of CS− in MSG group, but not in NaCl and glucose groups. After conditioned, the MSG group showed significantly higher intake and preference for CS+ solution (69.9%), while the NaCl and glucose group did not show any significant intake and preference for CS+ solution (50.9%, 43.5%, respectively). These results indicate that the amino acid l-glutamate at a preferable concentration has a positive postingestive effect as demonstrated by its ability to condition a flavor preference. The mechanism(s) for this positive effect could be through a direct effect on gut Glu receptors rather than the provision of calories or glucose from metabolized Glu; Further studies are needed to test these hypotheses.     

Amygdalar unit activity during three learning tasks: eyeblink classical conditioning, Pavlovian fear conditioning, and signaled avoidance conditioning

Neural activity in central and basolateral amygdala nuclei (CeA and BLA, respectively) was recorded during delay eyeblink conditioning, Pavlovian fear conditioning, and signaled barpress avoidance. During paired training, the CeA exhibited robust learning-related excitatory activity during all 3 tasks. By contrast, the BLA exhibited minimal activity during eyeblink conditioning, while demonstrating pronounced increases in learning-related excitatory responsiveness during fear conditioning and barpress avoidance. In addition, the relative amount of amygdalar activation observed appeared to be related to the relative intensity of the unconditioned stimulus and somatic requirements of the task. Results suggest the CeA mediates the Pavlovian association between sensory stimuli and the BLA mediates the modulation of instrumental responding through the assignment of motivational value to the unconditioned stimulus.     

Reinforcer-specificity of appetitive and consummatory behavior of rats after Pavlovian conditioning with food reinforcers

We examined the reinforcer-specificity of Pavlovian conditioning in the control of appetitive and consummatory behaviors in Pavlovian-to-instrumental transfer, cue-potentiated eating, and devaluation procedures. Rats received pairings of one conditioned stimulus with sucrose and another conditioned stimulus with maltodextrin. In Experiment 1, rats were also trained to earn sucrose for one instrumental response and maltodextrin for another. In a transfer test, the Pavlovian cues enhanced the rate of instrumental responding more when the food reinforcer predicted by the instrumental response and the Pavlovian cue were consistent than when they were inconsistent, but both cues enhanced both responses. In Experiment 2, sated rats' consumption of each food was potentiated in the presence of a cue for that food, but not in the presence of a cue for the other food. In Experiment 3, one food was devalued by pairing it with lithium chloride, prior to testing food consumption and food-cup directed behaviors. The food cues selectively controlled food-cup related behaviors, regardless of the presence of the devalued or nondevalued foods in the food cup. Together, these results are consistent with the view that conditioned cues modulate appetitive and consummatory behaviors with increasing levels of specificity. The closer an action comes to ingestion, the more it is controlled by sensory properties conveyed by learned cues. These data are discussed in the context of allostatic regulation of food foraging and intake.     

Tonic and Phasic Electrodermal Measures of Human Aversive Conditioning with Long Duration Stimuli

Two experiments investigated phasic and tonic electrodermal responding to long, variable-duration stimuli in aversive conditioning procedures. Experiment I demonstrated reliable differential conditioning on both phasic (first interval response, FIR) and tonic (change in skin conductance level, delta SCL; spontaneous fluctuations) measures, using 10-40-s slides as conditioned stimuli (CSs) and electric shock as the unconditioned stimulus (UCS). Experiment 2 examined the sensitivity of phasic and tonic measures to UCS aversiveness. Both FIR and delta SCL were greater to a conditioned stimulus paired with shock than one paired with an innocuous reaction-time warning tone. Responding was reversed when the reinforcement contingencies were reversed. It was suggested that, with long duration CSs and an aversive UCS, phasic measures to stimulus onset, such as FIR, may reflect both stimulus significance and threat appraisal, whereas tonic measures reflect primarily arousal or anxiety arising from anticipation of the aversive unconditioned stimulus.     

Flavor preferences conditioned by postingestive effects of nutrients in preweanling rats

The purpose of these experiments was to determine if preweanling rats, like adults, are capable of learning to associate an arbitrary flavor with the postingestive effects of nutrients, and then demonstrate a preference for that flavor after weaning. In Experiment 1, preweanlings were trained daily from postnatal day (P) 16 through P19 with intraoral (IO) infusions of a grape or cherry flavor (CS+) mixed with 20% glucose (US), and the opposite flavor (CS-) mixed with 0.05% saccharin. After weaning, rats were given a 4-h two-bottle choice between the CS+ and CS- flavors both presented in 0.05% saccharin. Rats preferred the flavor previously paired with glucose. In Experiment 2 using similar methods, rats learned to prefer a flavor (CS+G) paired with a glucose US over a flavor (CS+S) paired with a sweeter but less nutritive sucrose US, indicating involvement of postingestive reinforcement. In Experiment 3 preweanling rats with IO and intragastric (IG) catheters were trained with a CS+ flavor paired with IG nutrient infusion, and a CS- flavor paired with no IG infusion. These rats showed no flavor preference 3 days after weaning, but did significantly prefer the CS+ flavor over the CS- flavor 10 days after weaning. Together these experiments demonstrate that neural mechanisms for flavor-nutrient associations are developed before weaning, allowing young rats to learn associations between arbitrary flavors and nutritive consequences. Thus nutrient conditioning may be one way that early experience (such as flavors from the maternal diet transmitted in milk) influences later dietary preferences.     

Classical conditioning in the fetal rat with a long delay between presentation of CS and US

A single paired presentation of the artificial nipple and milk results in classical conditioning of changes in perioral responsiveness in the E20 rat fetus. This classical conditioning is evidenced by a reduction in responding to perioral tactile stimulation. The results of Experiment 1 confirmed the specificity of milk as an unconditioned stimulus to support classical conditioning. Experiment 2 demonstrated that single-trial classical conditioning with the artificial nipple CS and milk US was possible with a delay of 30 s between nipple and milk presentations. Further, measurements of fetal motor behavior during the delay between CS and US presentations indicated that a single 15-s presentation of the artificial nipple increased movements of the mouth for 30 s after removal of the artificial nipple. Experiment 3 demonstrated that three exposures to the artificial nipple prolonged the expression of mouthing for up to 120 s and made possible single trial classical conditioning with a delay of 120 s between CS and US presentations. The capacity of the fetal CNS to maintain a “behavioral trace” for an ecologically important stimulus, such as the nipple, could have adaptive significance in the early development of motivated behavior. © 1997 John Wiley & Sons, Inc. Dev Psychobiol 30: 49–59, 1997     

Appetitive-aversive interactions in Pavlovian fear conditioning

The existence of value coding and salience coding neurons in the mammalian brain, including in habenula and ventral tegmental area, has sparked considerable interest in the interactions that occur between Pavlovian appetitive and aversive conditioning. Here we studied these appetitive-aversive interactions at the behavioral level by assessing the learning that occurs when a Pavlovian appetitive conditioned stimulus (conditional stimulus, CS) serves as a CS for shock in Pavlovian fear conditioning. A Pavlovian appetitive CS was retarded in the rate at which it could be transformed into a fear CS (counterconditioning), but the presence of the appetitive CS augmented fear learning to a concurrently presented neutral CS (superconditioning). Retardation of fear learning was not alleviated by manipulations designed to restore the associability of the appetitive CS before fear conditioning but was alleviated by manipulations designed to increase the aversive quality of the shock unconditioned stimulus (US). These findings are consistent with opponent interactions between the appetitive and aversive motivational systems and provide a behavioral approach for assessing the neural correlates of these appetitive-aversive interactions.     

Facilitation of appetitive pavlovian conditioning by d-amphetamine in the shell,but not the core,of the nucleus accumbens

The effects of postsession d-amphetamine within subregions of the ventral and dorsal striatum on appetitive Pavlovian learning were assessed. Rats acquired a conditioned approach response on presentation of a stimulus predictive of 10% sucrose solution (unconditioned stimulus [US]), but not during equally frequent presentations of a stimulus uncorrelated with the US. In Experiment 1, postsession d-amphetamine infusions enhanced acquisition of conditioned responding, with no effect on control measures. In Experiment 2, rats received postsession d-amphetamine in the accumbens shell or core. Shell infusions facilitated conditioning; core infusions did not. In Experiment 3, dorsomedial striatal infusions of d-amphetamine also were ineffective. In sum, dopaminergic activation within the shell, but not the core, of the nucleus accumbens facilitates the acquisition of a Pavlovian association.     

Reconciling sensory cues and varied consequences of avian repellents

We learned previously that red-winged blackbirds (Agelaius phoeniceus) use affective processes to shift flavor preference, and cognitive associations (colors) to avoid food, subsequent to avoidance conditioning. We conducted three experiments with captive red-winged blackbirds to reconcile varied consequences of treated food with conditioned sensory cues. In Experiment 1, we compared food avoidance conditioned with lithium chloride (LiCl) or naloxone hydrochloride (NHCl) to evaluate cue-consequence specificity. All blackbirds conditioned with LiCl (gastrointestinal toxin) avoided the color (red) and flavor (NaCl) of food experienced during conditioning; birds conditioned with NHCl (opioid antagonist) avoided only the color (not the flavor) of food subsequent to conditioning. In Experiment 2, we conditioned experimentally naïve blackbirds using free choice of colored (red) and flavored (NaCl) food paired with an anthraquinone- (postingestive, cathartic purgative), methiocarb- (postingestive, cholinesterase inhibitor), or methyl anthranilate-based repellent (preingestive, trigeminal irritant). Birds conditioned with the postingestive repellents avoided the color and flavor of foods experienced during conditioning; methyl anthranilate conditioned only color (not flavor) avoidance. In Experiment 3, we used a third group of blackbirds to evaluate effects of novel comparison cues (blue, citric acid) subsequent to conditioning with red and NaCl paired with anthraquinone or methiocarb. Birds conditioned with the postingestive repellents did not avoid conditioned color or flavor cues when novel comparison cues were presented during the test. Thus, blackbirds cognitively associate pre- and postingestive consequences with visual cues, and reliably integrate visual and gustatory experience with postingestive consequences to procure nutrients and avoid toxins.     

Impact of healthy aging on awareness and fear conditioning

Fear conditioning has provided a useful model system for studying associative emotional learning, but the impact of healthy aging has gone relatively unexplored. The present study investigated fear conditioning across the adult life span in humans. A delay discrimination task was employed using visual conditioned stimuli and an auditory unconditioned stimulus. Awareness of the reinforcement contingencies was assessed in a postexperimental interview. Compared with young adult participants, middle-aged and older adults displayed reductions in unconditioned responding, discriminant conditioning, and contingency awareness. When awareness and overall arousability were taken into consideration, there were no residual effects of aging on conditioning. These results highlight the importance of considering the influence of declarative knowledge when interpreting age-associated changes in discriminative conditioned learning.     

The suppressive effects of LiCl, sucrose, and drugs of abuse are modulated by sucrose concentration in food-deprived rats.

Suppression of intake of a gustatory conditioned stimulus (CS) occurs when paired with either an aversive or an appetitive unconditioned stimulus (US). Toxic substances, such as lithium chloride (LiCl), induce conditioned taste aversions while rewarding stimuli, such as high a concentration of sucrose, reduce intake through a comparison process referred to as anticipatory contrast. Drugs of abuse also suppress CS intake, but it is not known whether they do so via their rewarding or aversive properties. Using 0.1, 0.3, or 0.5 M sucrose solutions as the gustatory CS, we compared the suppressive effects of LiCl (5.29 mg/kg), morphine (15 mg/kg), cocaine (10 mg/kg), and a 1.0-M sucrose solution in rats that were food deprived. The doses of the three drugs have been equated in terms of their suppressive effects in water-deprived and free-feeding rats. The results showed that in food-deprived rats the sucrose US failed to suppress intake of any of the sucrose CSs, the drugs of abuse failed to suppress intake of the 0.3 and 0.5-M concentration of sucrose, and LiCl failed to suppress intake of the 0.5-M sucrose solution. When taken together, these findings reveal that the suppressive effects of all USs (aversive, appetitive, and drugs of abuse) can be offset by the use of a caloric CS when evaluated in food-deprived rats.     

Stimulus processing and associative learning in Wistar and WKHA rats

This study assessed basic learning and attention abilities in Wistar-Kyoto hyperactive (WKHA) rats using appetitive conditioning preparations. Two measures of conditioned responding to a visual stimulus, orienting behavior (rearing on the hind legs), and food cup behavior (placing the head inside the recessed food cup) were measured. In Experiment 1, simple conditioning, but not extinction, was impaired in WKHA rats compared with Wistar rats. In Experiment 2, nonreinforced presentations of the visual cue preceded the conditioning sessions. WKHA rats displayed less orienting behavior than Wistar rats but comparable levels of food cup behavior. These data suggest that WKHA rats exhibit specific abnormalities in attentional processing as well as in learning stimulus-reward relationships.     

Classical conditioning in the rat fetus: involvement of mu and kappa opioid systems in the conditioned response

When the Embryonic Day 20 (E20) rat fetus is given a conditioning trial involving a paired presentation of an artificial nipple (the conditioned stimulus; CS) with an intraoral infusion of milk (the unconditioned stimulus; US), it shows evidence of classical conditioning when again exposed to the CS during a test trial. Specifically, the fetus shows fewer oral grasp responses (the conditioned response; CR) when continuously presented with the artificial nipple. The present study further investigated this classically conditioned reduction in oral grasping. Separate experiments (a) examined the time course of the reduction in oral grasping (Experiment 1), (b) characterized the time course of mu opioid (Experiment 2) and kappa opioid (Experiment 3) involvement in the CR, and (c) described changes in fetal behavior (Experiment 4) associated with mu and kappa opioid effects on responding to the artificial nipple. The results are discussed in terms of opioid involvement in establishing and maintaining early suckling behavior.     

Effects of sibutramine on the appetitive and consummatory aspects of feeding in non-human primates

This study examined how sibutramine (0.06-4.0 mg/kg, i.m.), a clinically effective weight-loss medication which increases extracellular serotonin and norepinephrine levels, affected the appetitive and consummatory aspects of feeding of non-human primates. The effects were compared to the effects of the positive control dexfenfluramine (2.0-6.0 mg/kg, p.o.), which primarily increases extracellular serotonin levels. Baboons had access to food 24 h each day, but they had to complete a two-phase operant procedure in order to eat. Responding on one lever during a 30-min appetitive phase was required before animals could start a consumption phase, where responding on another lever led to food delivery, i.e., a meal. Responding during the appetitive phase resulted in presentations of food-related stimuli only. Sibutramine increased the latency to the first meal of the session in females, and decreased consummatory behavior without affecting other appetitive behavior in males and females. In contrast, dexfenfluramine, increased the latency to the first meal of the session, and decreased both appetitive and consummatory behavior in males and females. The behavioral mechanism by which sibutramine decreases food intake is distinct from other anorectic drugs, including dexfenfluramine, that have been tested in this paradigm.     

Acquisition of classically conditioned-related activity in the hippocampus is affected by lesions of the cerebellar interpositus nucleus

Rabbits were first given left cerebellar interpositus nucleus lesions followed by classical nictitating membrane (NM) conditioning using paired presentations of a tone conditioned stimulus and an air puff unconditioned stimulus. Multiple-unit hippocampal activity was monitored over the course of training. In rabbits with anterior interpositus lesions, the acquisition of learned responses and significant increases in training-related hippocampal activity were prevented when paired training was given to the left NM but not when training was switched to the right NM. Rabbits with lesions anterior to the interpositus or in surrounding cerebellar regions failed to show deficits in behavioral responding or hippocampal activity. These results indicate that acquisition of conditioning-related activity in the hippocampus depends on an intact interpositus nucleus of the cerebellum.     

Conditioned enhancement of flavor evaluation reinforced by intragastric glucose. II. Taste reactivity analysis.

Rats learn to prefer a flavor that is paired with intragastric (IG) glucose infusion, which may represent a learned shift in the hedonic evaluation or palatability of the flavor. The present study used the taste reactivity (TR) test to infer nutrient-conditioned changes in flavor palatability. Rats were first conditioned in 20-h/day and then 30-min/day sessions to associate a flavored saccharin solution (the CS+) with IG infusions of 16% glucose, and a different flavored saccharin solution (the CS-) with IG water infusions. They strongly preferred the CS+ to the CS- in two-bottle intake tests. When next tested with brief intraoral (IO) infusions of the CS flavors, the rats exhibited significantly more hedonic TR responses to the CS+ flavor than the CS- flavor, which indicates an enhanced hedonic evaluation. A subsequent series of two-bottle tests established that the CS- flavor was equally preferred to 3% fructose, whereas the CS+ flavor was equally preferred to 16% fructose. In addition, the difference between the TR responses to 3% and 16% fructose paralleled the difference between the TR responses to CS- and CS+. These findings support the idea that pairing flavored saccharin with the postingestive effects of glucose produces a learned shift in palatability comparable to that produced by increasing the concentration of a sugar solution.     

The suppressive effects of sucrose and cocaine, but not lithium chloride, are greater in Lewis than in Fischer rats: evidence for the reward comparison hypothesis

Rats suppress intake of a saccharin conditioned stimulus (CS) when it is paired with an aversive unconditioned stimulus (US), an appetitive US, or a drug of abuse such as morphine or cocaine. It is unclear, however, whether the reduction in intake induced by these drugs is mediated by their aversive or their rewarding properties. The present set of experiments addressed this question by comparing the suppressive effects of a known aversive US (LiCl), a known reinforcing US (sucrose), and a drug of abuse (cocaine) in two strains of rats (i.e., Lewis and Fischer 344 rats) that differ in their preference for rewarding stimuli. The results show that, although both strains readily acquired a LiCl-induced conditioned taste aversion (CTA), the suppressive effects of sucrose and cocaine were robust in the drug-preferring Lewis rats and absent in the Fischer rats. These data argue against a CTA account and in favor of the reward comparison hypothesis.     

Sucrose taste but not Polycose taste conditions flavor preferences in rats

Rats have an inborn preference for sweet taste and learn to prefer flavors associated with sweetness. They are also strongly attracted to the taste of glucose polymers (e.g., Polycose). This "poly" taste differs in quality from the sweet taste of sugar. To determine if poly taste, like sweet taste, conditions flavor preferences rats were trained with a distinctive flavor (CS+) added to 2% Polycose solution and a different flavor (CS-) added to plain water. In a subsequent two-bottle test the rats did not prefer the CS+ to CS- when both flavors were presented in water. In contrast, other rats significantly preferred a CS+ flavor that had been paired with 2% sucrose. Adding saccharin to a flavored Polycose solution did not improve CS+ flavor learning; rather, Polycose appeared to overshadow saccharin-induced conditioning. Flavor conditioning by a 16% Polycose solution was assessed using a sham-feeding procedure to prevent post-oral reinforcement. Although the rats sham-fed substantial amounts of the CS+ flavored Polycose solution, they failed to prefer the CS+ to the CS- flavor. This contrasts with the preference other rats displayed for a CS+ paired with sham-fed sucrose. Why attractive sweet and poly tastes differ in their ability to condition flavor preferences is not certain, although some findings suggest that they differentially activate dopamine and/or serotonin circuits involved in flavor learning.