Consummatory Responses Research Articles

Pavlovian cue-evoked alcohol seeking is disrupted by ventral pallidal inhibition

Cues paired with alcohol can be potent drivers of craving, alcohol-seeking, consumption, and relapse. While the ventral pallidum is implicated in appetitive and consummatory responses across several reward classes and types of behaviors, its role in behavioral responses to Pavlovian alcohol cues has not previously been established. Here, we tested the impact of optogenetic inhibition of ventral pallidum on Pavlovian-conditioned alcohol-seeking in male Long Evans rats. Rats underwent Pavlovian conditioning with an auditory cue predicting alcohol delivery to a reward port and a control cue predicting no alcohol delivery, until they consistently entered the reward port more during the alcohol cue than the control cue. We then tested the within-session effects of optogenetic inhibition during 50% of cue presentations. We found that optogenetic inhibition of ventral pallidum during the alcohol cue reduced port entry likelihood and time spent in the port, and increased port entry latency. Overall, these results suggest that normal ventral pallidum activity is necessary for Pavlovian alcohol-seeking.

Flexible Behavioral Adjustment to Frustrative Nonreward in Anticipatory Behavior, but Not in Consummatory Behavior, Requires the Dorsal Hippocampus.

The hippocampus (HC) is recognized for its pivotal role in memory-related plasticity and facilitating adaptive behavioral responses to reward shifts. However, the nature of its involvement in the response to reward downshifts remains to be determined. To bridge this knowledge gap, we explored the HC's function through a series of experiments in various tasks involving reward downshifts and using several neural manipulations in rats. In Experiment 1, complete excitotoxic lesions of the HC impaired choice performance in a modified T-maze after reducing the quantity of sugar pellet rewards. In Experiment 2, chemogenetic inhibition of the dorsal HC (dHC) disrupted anticipatory behavior following a food-pellet reward reduction. Experiments 3-5 impaired HC function by using peripheral lipopolysaccharide (LPS) administration. This treatment, which induces peripheral inflammation affecting HC function, significantly increased cytokine levels in the dHC (Experiment 3) and impaired anticipatory choice behavior (Experiment 4). None of these dorsal hippocampal manipulations affected consummatory responses in animals experiencing sucrose downshifts. Accordingly, we found no evidence of increased neural activation in either the dorsal or ventral HC, as measured by c-Fos expression, after a sucrose downshift task involving consummatory suppression (Experiment 6). The results highlight the HC's pivotal role in adaptively modulating anticipatory behavior in response to a variety of situations involving frustrative nonreward, while having no effect on adjustments on consummatory behavior. The data supporting this conclusion were obtained under heterogeneous experimental conditions derived from a multi-laboratory collaboration, ensuring the robustness and high reproducibility of our findings. Spatial orientation, memory update, choice of reward signals of different values, and anticipatory versus consummatory adjustments to reward downshift are discussed as potential mechanisms that could account for the specific effects observed from HC manipulations.

The conserved endocannabinoid anandamide modulates olfactory sensitivity to induce hedonic feeding in C. elegans

The ability of cannabis to increase food consumption has been known for centuries. In addition to producing hyperphagia, cannabinoids can amplify existing preferences for calorically dense, palatable food sources, a phenomenon called hedonic amplification of feeding. These effects result from the action of plant-derived cannabinoids that mimic endogenous ligands called endocannabinoids. The high degree of conservation of cannabinoid signaling at the molecular level across the animal kingdom suggests hedonic feeding may also be widely conserved. Here, we show that exposure of Caenorhabditis elegans to anandamide, an endocannabinoid common to nematodes and mammals, shifts both appetitive and consummatory responses toward nutritionally superior food, an effect analogous to hedonic feeding. We find that anandamide's effect on feeding requires the C.elegans cannabinoid receptor NPR-19 but can also be mediated by the human CB1 cannabinoid receptor, indicating functional conservation between the nematode and mammalian endocannabinoid systems for the regulation of food preferences. Furthermore, anandamide has reciprocal effects on appetitive and consummatory responses to food, increasing and decreasing responses to inferior and superior foods, respectively. Anandamide's behavioral effects require the AWC chemosensory neurons, and anandamide renders these neurons more sensitive to superior foods and less sensitive to inferior foods, mirroring the reciprocal effects seen at the behavioral level. Our findings reveal a surprising degree of functional conservation in the effects of endocannabinoids on hedonic feeding across species and establish a new system to investigate the cellular and molecular basis of endocannabinoid system function in the regulation of food choice.

Early-life low-calorie sweetener consumption disrupts glucose regulation, sugar-motivated behavior, and memory function in rats.

Low-calorie sweetener (LCS) consumption in children has increased dramatically due to its widespread presence in the food environment and efforts to mitigate obesity through sugar replacement. However, mechanistic studies on the long-term impact of early-life LCS consumption on cognitive function and physiological processes are lacking. Here, we developed a rodent model to evaluate the effects of daily LCS consumption (acesulfame potassium, saccharin, or stevia) during adolescence on adult metabolic, behavioral, gut microbiome, and brain transcriptomic outcomes. Results reveal that habitual early-life LCS consumption impacts normal postoral glucose handling and impairs hippocampal-dependent memory in the absence of weight gain. Furthermore, adolescent LCS consumption yielded long-term reductions in lingual sweet taste receptor expression and brought about alterations in sugar-motivated appetitive and consummatory responses. While early-life LCS consumption did not produce robust changes in the gut microbiome, brain region-specific RNA-Seq analyses reveal LCS-induced changes in collagen- and synaptic signaling-related gene pathways in the hippocampus and nucleus accumbens, respectively, in a sex-dependent manner. Collectively, these results reveal that habitual early-life LCS consumption has long-lasting implications for glucoregulation, sugar-motivated behavior, and hippocampal-dependent memory in rats, which may be based in part on changes in nutrient transporter, sweet taste receptor, and central gene pathway expression.

Increment in the consummatory response induced by reward delay: An animal model of binge-like eating episodes

The omission of an expected palatable reinforcer produces an aversive emotional state, called frustration, that could function as an important factor in the etiology and maintenance of the binge-eating disorder. A series of experiments carried out in adult male Wistar rats are presented, in which the consummatory response of sugary drinks was evaluated after events of frustration due to reward delay. The animals were trained in a consummatory behavior acquisition phase, in which they had access to different concentrations of sucrose solutions. In the test phase, a control group received the reinforcer normally, while an experimental group received it after a delay. A significant increase in the consummatory behavior of a 32 % sucrose was found in the group that was exposed to a 2-min delay before re-introducing the reinforcer (Experiment 1). The increment found in the consummatory response was dependent on the aversive state of frustration. This could be concluded because, in a less frustrating condition, the animals did not exhibit the phenomenon (Experiment 2), and a more frustrating one produced an increment of the effect (Experiment 3). This result was also observed using a direct measure of consumption -kilocalorie intake- during several events of reinforcement delay (Experiment 4).

Connecting animal trainers and behavior analysts through loopy training.

The communities of behavior analysts and animal trainers remain relatively disconnected despite potentially beneficial links between behavioral principles and the practices of animal training. Describing existing links between research by behavior analysts and practices used by animal trainers may foster connections. In this paper, we describe an approach used by many clicker trainers, referred to as loopy training. Loopy training is a teaching process built around the concept of movement cycles. Interactions between the animal learner and the handler are refined into predictable, cyclical patterns that can be expanded into complex sequences. These sequences include cues, target responses, conditioned reinforcers, and consummatory responses. We link the foundations of loopy training to existing work in the experimental analysis of behavior, compare loopy training to other shaping approaches, and describe areas for future research. We conclude with a series of recommendations for further developing connections between behavior analysts and animal trainers, using loopy training as the foundation for our suggestions.

A Subregion of Insular Cortex Is Required for Rapid Taste-Visceral Integration and Consequent Conditioned Taste Aversion and Avoidance Expression in Rats.

Postingestive signals are important for shaping appetitive and consummatory responses, but the brain mechanisms required to assimilate interoceptive events with those at the frontlines of ingestion (taste-guided) are poorly understood. Here, we investigated whether an insular cortex (IC) region, which receives viscerosensory input, including gustatory, is required to modify taste-elicited consummatory reactions in response to a real-time interoceptive change using a serial taste reactivity (TR) test where the rats’ oromotor and somatic reactions to intraoral (IO) infusions of sucrose were periodically assessed over 45 min following lithium chloride (LiCl) administration. Results showed that neurally-intact rats shifted from an ingestive repertoire to an aversive one as LiCl took effect. Overall, this hedonic shift was delayed in rats with bilateral neurotoxic IC lesions. Rats with greater neuronal loss in posterior gustatory IC displayed fewer aversive reactions to sucrose following this initial LiCl injection. We further assessed whether the failure to integrate interoceptive feedback with ongoing taste-guided behavior impaired acquisition and/or expression of conditioned aversion and/or avoidance in these same rats. Although, as a group, LiCl-injected rats with IC lesions subsequently avoided the sugar in a 48-h two-bottle test, their preference for sucrose was significantly greater than that of the LiCl-injected neurally-intact rats. Overall lesion size, as well as proportion of the posterior gustatory and/or anterior visceral IC were each associated with impaired avoidance. These findings reveal new roles for the posterior gustatory and anterior visceral ICs in multisensory integrative function.

Anticipatory and Consummatory Responses to Touch and Food Rewards: A Protocol for Human Research.

Understanding the neural basis of reward processing is a major concern, as it holds the key to alleviating symptoms of addiction and poor mental health. However, this goal seems difficult to attain as long as research on reward processing cannot easily be compared across species and reward types, due to methodological differences and the presence of confounding factors. We recently developed an experimental paradigm that allows monitoring anticipatory and consummatory responses to matched social (touch) and nonsocial (food) rewards in adult humans. The following protocol describes in detail the materials and the paradigm, which measures reward wanting and liking with a real effort task and subjective ratings. It can also be used in combination with facial electromyography (EMG), brain imaging (e.g., fMRI), and pharmacological interventions. It is our firm belief that the field will profit greatly from more research being conducted on reward processing using this and similarly controlled paradigms, which allow for cross-species comparison.

Increased neuronal activity of serotonin neurons in the median raphe nucleus attenuates reward-related consummatory responses and facial expression

Increased neuronal activity of serotonin neurons in the median raphe nucleus attenuates reward-related consummatory responses and facial expression

An endogenous opioid circuit determines state-dependent reward consumption.

µ-Opioid peptide receptor (MOPR) stimulation alters respiration, analgesia and reward behaviour, and can induce substance abuse and overdose1-3. Despite its evident importance, the endogenous mechanisms for MOPR regulation of consummatory behaviour have remained unknown4. Here we report that endogenous MOPR regulation of reward consumption in mice acts through a specific dorsal raphe to nucleus accumbens projection. MOPR-mediated inhibition of raphe terminals is necessary and sufficient to determine consummatory response, while select enkephalin-containing nucleus accumbens ensembles are engaged prior to reward consumption, suggesting that local enkephalin release is the source of the endogenous MOPR ligand. Selective modulation of nucleus accumbens enkephalin neurons and CRISPR-Cas9-mediated disruption of enkephalin substantiate this finding. These results isolate a fundamental endogenous opioid circuit for state-dependent consumptive behaviour and suggest alternative mechanisms for opiate modulation of reward.

The insulo-opercular cortex encodes food-specific content under controlled and naturalistic conditions

The insulo-opercular network functions critically not only in encoding taste, but also in guiding behavior based on anticipated food availability. However, there remains no direct measurement of insulo-opercular activity when humans anticipate taste. Here, we collect direct, intracranial recordings during a food task that elicits anticipatory and consummatory taste responses, and during ad libitum consumption of meals. While cue-specific high-frequency broadband (70–170 Hz) activity predominant in the left posterior insula is selective for taste-neutral cues, sparse cue-specific regions in the anterior insula are selective for palatable cues. Latency analysis reveals this insular activity is preceded by non-discriminatory activity in the frontal operculum. During ad libitum meal consumption, time-locked high-frequency broadband activity at the time of food intake discriminates food types and is associated with cue-specific activity during the task. These findings reveal spatiotemporally-specific activity in the human insulo-opercular cortex that underlies anticipatory evaluation of food across both controlled and naturalistic settings.

Evidence of hypoglycemic anhedonia and modulation by bupropion in rats

BackgroundDisorders characterized by dysfunction of glucose metabolism are often comorbid with depression. The current study investigated whether a hypoglycemic state caused by 2-deoxy-d-glucose (2-DG) can result in anhedonic behaviors responsive to stimulation of monoamine activity. MethodsIn experiment 1, male Sprague-Dawley rats were tested for maintenance of intra-oral self-administration (IOSA) of a sweet solution after pre-treatment with 300 or 500 mg/kg 2-DG, a blocker of glucose metabolism. Experiment 2 determined whether exposure to an environment previously paired with the effects of 2-DG (0, 200 or 300 mg/kg) can influence IOSA, and whether 2-DG can modify taste reactivity to same sweet solution. Finally, experiment 3 examined whether 0 or 30 mg/kg bupropion, a monoamine-reuptake blocker, would attenuate the effect of 300 mg/kg 2-DG on IOSA and taste reactivity. ResultsIt was found that 2-DG produced a sustained decrease in IOSA when animals were tested drug-free. This decrease in IOSA did not appear linked to place conditioning or to alterations in taste reactivity, and it was partially normalized by pre-treatment with bupropion. ConclusionsTaken together, these results in rats suggest that rapid hypoglycemia can induce an anhedonic state characterized by impaired consummatory responses to nutritional incentive stimuli and that can be alleviated by the antidepressant bupropion.

Compulsive Conditioned Sexual Responding of Male Japanese Quail in Extinction.

Previous experiments showed that following acquisition of an association between a terry-cloth object conditioned stimulus (CS) and a live female unconditioned stimulus (US), male quail increased the frequency of their copulations with the inanimate CS during subsequent CS-alone (extinction) trials. The present experiment was conducted to identify the potential factors responsible for this unexpected increase in conditioned sexual behavior during extinction. A total of 57 naïve male quail were given pairings of a terry-cloth CS with a live female during acquisition. A total of 36 of these quail (the approach responders) showed only conditioned approach response to the CS object, whereas the remaining 21 quail (the consummatory responders) also displayed copulatory or consummatory responses to the CS. In the extinction phase, these two sets of quail were divided into two subgroups: one subgroup received a female in their home cages while the other did not. Consummatory responders that were not exposed to a female quail in the home cage showed a significant increase in conditioned consummatory responding as the extinction trials progressed (i.e., compulsive conditioned sexual responding), whereas the other subgroup showed no change. However, both subgroups showed resistance to extinction in both conditioned approach and consummatory behavior. These findings indicate that the increase in copulation with the terry-cloth CS during extinction is possibly caused by US deprivation. The findings also suggest that conditioned copulation with the terry-cloth CS may lead to partial drive satisfaction, which may contribute to persistence of the behavior. Implications of these findings for paraphilias and compulsive sexual behavior are discussed.

Diferencias fenotípicas ante la devaluación y omisión de una recompensa esperada

La frustración es una respuesta comportamental, emocional y neurobiológica concomitante a la discrepancia negativa entre el refuerzo esperado y el obtenido, ya sea por la devaluación u omisión del incentivo. Los modelos animales y la comparación de cepas endocriadas han permitido estudiar la contribución de los factores genéticos a la expresión de diferencias fenotípicas en tales situaciones. El objetivo consistió en comparar cepas que difieren en su comportamiento emocional ante la devaluación (Exp 1) y omisión (Exp 2) de un refuerzo: las ratas espontáneamente hipertensas (SHR) y normotensas Wistar Kyoto (WKY). En ambos experimentos se halló que las SHR realizaron significativamente más respuestas de ingesta durante la fase de adquisición. En la fase de prueba del Exp 1, se observó una recuperación enlentecida de su respuesta. En el Exp 2 no se observaron diferencias entre cepas. La cepa emocionalmente más reactiva (SHR) no difirió con respecto a su control (WKY) en la reacción inicial ante la devaluación del refuerzo, pero mostró una recuperación enlentecida. Estos datos son congruentes con la literatura que sugiere que, ante la devaluación del incentivo, las diferencias fenotípicas se expresan con mayor facilidad en la recuperación de la respuesta (frustración secundaria).

Hold-down as an alternative to unit dose in cocaine self-administration experiments: Characterization using a progressive ratio schedule.

Virtually all cocaine self-administration studies have used a "unit dose" as a reinforcing stimulus; the subject is a passive recipient of an experimenter-selected dose. The present experiments examined the consequence of requiring the subject to actively determine the dose and speed of each injection. A two-lever procedure was used in which responding on a progressive ratio (PR) schedule provided access to cocaine on a hold down (HD) schedule. With HD, the pump is turned on for the duration that the lever is held down, thus the dose and speed of injection is determined by the behavior of the subject. The procedure allows for the evaluation of both drug taking and drug seeking responses. The results were qualitatively different from PR self-administration studies using unit dose. The self-administered HD dose varied across the session; the self-administered dose was found to inversely correlate with drug levels at the time of access. Importantly, the 2 L-PR-HD procedure identified a subpopulation of subjects that showed extremes in both drug seeking and drug taking. Subjects at the top end of the distribution displayed unprecedented final ratios (> 900) and rapidly self-administered very large doses (> 1.4 mg; ~ 4.2 mg/kg). Manipulation of drug-taking variables (HD access duration and concentration of drug in the pump) showed that the immediacy of a cocaine bolus, not the duration of access, is the major determinant of drug seeking. Incorporating a consummatory response into a PR procedure provides a unique perspective on the interactions of drug-seeking and drug-taking.

Intravenous and oral caffeine self-administration in rats

Caffeine is widely consumed for its psychoactive effects worldwide. No pre-clinical study has established reliable caffeine self-administration, but we found that caffeine can enhance the reinforcing effects of non-drug rewards. The goal of the present studies was to determine if this effect of caffeine could result in reliable caffeine self-administration. In 2 experiments rats could make an operant response for caffeine delivered in conjunction with an oral ‘vehicle’ including saccharin (0.2% w/v) as a primary reinforcer. In Experiment 1, intravenous (IV) caffeine infusions were delivered in conjunction with oral saccharin for meeting the schedule of reinforcement. In control conditions, oral saccharin alone or presentations of IV caffeine alone served as the reinforcer. In Experiment 2, access to caffeine was provided in an oral vehicle containing water, decaffeinated instant coffee (0.5% w/v), or decaffeinated coffee and saccharin (0.2%). The concentration of oral caffeine was then manipulated across testing sessions. Oral and IV caffeine robustly increased responding for saccharin in a manner that was repeatable, reliable, and systematically related to unit IV dose. However, the relationship between oral caffeine dose and operant behavior was less systematic; the rats appeared to titrate their caffeine intake by reducing the consummatory response (drinking) rather than the appetitive response (lever pressing). These studies establish reliable volitional caffeine self-administration in rats. The reinforcement enhancing effects of caffeine may help to explain widespread caffeine use by humans, who ingest caffeine in complex vehicles with reinforcing properties.

Maternal manipulation during late gestation (GDs 17-20) enhances ethanol consumption and promotes changes and opioid mRNA expression in infant rats

Fetal ethanol experience generates learning and memories capable to increase ethanol consummatory behaviors during infancy. Opioid system seems to be involved in mediating those alcohol-related behaviors. In this work, we proposed to study the impact of prenatal exposure to a moderate ethanol dose, upon ingestion of the drug and possible ethanol-induced molecular changes on opioid precursor peptides (POMC, Pro-enk and Pro-DYN) and receptors (MOR, DOR and KOR) mRNA expression, in hypothalamus. Pregnant rats received during gestational days (GDs) 17-20, a daily intragastric (i.g.) administration with 2g/kg ethanol or water. A third group of dams was left undisturbed during pregnancy (Unmanipulated group). Intake test was conducted at postnatal days (PDs) 14-15. Three groups of pups were performed: control (no intake test), water (vehicle) and 5% ethanol. At the end of intake test blood samples were taken to quantify blood ethanol concentrations (BECs) and hypothalamus sections were obtained to perform qRT-PRC assessment of opioid precursor peptides and receptors. The analysis of the consummatory responses (% of consumption) and pharmacokinetic profiles (BECs) suggested that maternal manipulation induced by i.g. intubations, during the last four days of gestation (whenever ethanol or water), are sufficient to induce infantile ethanol intake during infancy. Gene expression from the hypothalamus of unmanipulated group revealed that infantile ingestive experiences with ethanol can down-regulate expression of mRNA Pro-Dyn and up-regulate mRNA expression of MOR and KOR. Finally, MOR mRNA expression was attenuated by prenatal i.g. manipulation in pups exposed to 5% ethanol.

Response-inhibition capacity in spontaneously hypertensive and Wistar rats: acquisition of fixed minimum interval performance and responsiveness to D-amphetamine.

Reduced response-inhibition capacity is a defining feature of attention-deficit hyperactivity disorder. The fixed minimum interval (FMI) schedule has been systematically validated to assess such capacity in rats. On each FMI trial, the first lever press initiates an inter-response time (IRT); a potentially consummatory response terminates the IRT; only IRTs longer than a target interval result in access to food. Despite task validity, steady-state FMI performance in the most common animal model of attention-deficit hyperactivity disorder, the spontaneously hypertensive rat (SHR), is similar to normotensive control performance, even though SHR performs at lower levels, especially during acquisition, in similar response-withholding tasks. To determine whether such limitations of the model are specific to stable-state performance, this experiment compared FMI 6-s performance in SHR and Wistar rats during acquisition and in steady state, and assessed the effect of acute D-amphetamine (AMP) administration (0.1, 0.5, and 1.0 mg/kg) on steady-state performance. Median latencies to first lever press were consistently shorter in SHR than in Wistar rats; IRTs were shorter for SHR than for Wistar rats during acquisition, but substantially less so during asymptotic performance. AMP dose-dependently reduced latencies, shortened IRTs, and, at the highest dose, increased the proportion of IRTs under schedule control. These results suggest that, relative to Wistar rats, SHR have a reduced capacity to learn to withhold a reinforced response; once the FMI is acquired, high doses of D-AMP disrupt withholding performance in both strains, but they also enhance the responsiveness of both strains to reinforcement contingencies.

Control of habitual instrumental actions by anticipation of postingestive sensations.

In animal behavioral experiments, extended training causes instrumental actions that deliver ingestible substances to lose sensitivity to outcome devaluation and contingency degradation, and to gain direct sensitivity to the current motivational state. These features of habitual control have been attributed to a process that relies on stimulus-response (S-R) associations linking the context to instrumental actions and Pavlovian associations linking the same context to orally-sensed properties of substances attained there. This Pavlovian process was conceived based on the results of irrelevant incentive experiments, but it is not supported by the results of all such experiments. An alternative process is therefore proposed here. In this process, recall of the instrumental action is evoked by an S-R association, but the rate at which this action is then performed is controlled by anticipation of postingestive sensations that have frequently followed it. This anticipation relies on recall of an association linking the action directly to the postingestive sensations. This association is learned during the formation of a chunked action series that begins with the instrumental action and ends with a consummatory response. It enables a prediction of subjective value that is directly influenced by the current motivational state, but is not influenced by devaluation or non-contingent delivery of the substance that has produced the postingestive sensations.

Two profiles in the recovery of reward devaluation in rats: Latent class growth analysis

Consummatory successive negative contrast (cSNC) occurs when animals exposed to an unexpected downshift from a high palatable reward (e.g., 32% sucrose solution) to a less preferred one (e.g., 4% sucrose solution) show an abrupt and transient suppression of the consummatory response, compared with control animals that always had access to the less preferred one. This phenomenon constitutes an animal model of stress produced by frustrative events. To obtain information about individual differences regarding cSNC, we used Latent Class Growth Analysis (LCGA) to analyze a sample of 53 animals exposed to an incentive downshift. We found two profiles of animals, both showing the suppression of the consummatory response but diverging in the speed of the recovery. Our results are consistent with previous literature showing individual differences in cSNC and do not support the existence of a third profile.