Appetitive Motivation Research Articles

Aversive Learning and Appetitive Motivation Toggle Feed-Forward Inhibition in the Drosophila Mushroom Body

SummaryIn Drosophila, negatively reinforcing dopaminergic neurons also provide the inhibitory control of satiety over appetitive memory expression. Here we show that aversive learning causes a persistent depression of the conditioned odor drive to two downstream feed-forward inhibitory GABAergic interneurons of the mushroom body, called MVP2, or mushroom body output neuron (MBON)-γ1pedc>α/β. However, MVP2 neuron output is only essential for expression of short-term aversive memory. Stimulating MVP2 neurons preferentially inhibits the odor-evoked activity of avoidance-directing MBONs and odor-driven avoidance behavior, whereas their inhibition enhances odor avoidance. In contrast, odor-evoked activity of MVP2 neurons is elevated in hungry flies, and their feed-forward inhibition is required for expression of appetitive memory at all times. Moreover, imposing MVP2 activity promotes inappropriate appetitive memory expression in food-satiated flies. Aversive learning and appetitive motivation therefore toggle alternate modes of a common feed-forward inhibitory MVP2 pathway to promote conditioned odor avoidance or approach.

NMDA Receptors on Dopaminoceptive Neurons Are Essential for Drug-Induced Conditioned Place Preference.

Plasticity of the brain’s dopamine system plays a crucial role in adaptive behavior by regulating appetitive motivation and the control of reinforcement learning. In this study, we investigated drug- and natural-reward conditioned behaviors in a mouse model in which the NMDA receptor-dependent plasticity of dopaminoceptive neurons was disrupted. We generated a transgenic mouse line with inducible selective inactivation of the NR1 subunit in neurons expressing dopamine D1 receptors (the NR1D1CreERT2 mice). Whole-cell recordings of spontaneous EPSCs on neurons in the nucleus accumbens confirmed that a population of neurons lacked the NMDA receptor-dependent component of the current. This effect was accompanied by impaired long-term potentiation in the nucleus accumbens and in the CA1 area of the ventral, but not the dorsal, hippocampus. Mutant mice did not differ from control animals when tested for pavlovian or instrumental conditioning. However, NR1D1CreERT2 mice acquired no preference for a context associated with administration of drugs of abuse. In the conditioned place preference paradigm, mutant mice did not spend more time in the context paired with cocaine, morphine, or ethanol, although these mice acquired a preference for sucrose jelly and an aversion to naloxone injections, as normal. Thus, we observed that the selective inducible ablation of the NMDA receptors specifically blocks drug-associated context memory with no effect on positive reinforcement in general.

Lu pour vous

Oxytocin (OT) systems contribute to the elicitation of stereotypic maternal behaviors. OT peptide-expressing neurons are predominantly localized in the hypothalamus, whereas OT receptor (OTR)-expressing neurons are widely distributed throughout the brain. Among those OTR-expressing regions, the paraventricular thalamus (PVT) consists of heterogeneous neuropeptide-responsive neurons critical for appetitive motivation, food intake control, and social behaviors; however, the precise distribution of OTR-expressing neurons within the PVT and whether these neurons are involved in maternal behaviors in mice are unknown. The distribution of OTR-expressing neurons was examined in an OTR-Venus transgenic line expressing a fluorescent protein controlled by the OTR promoter. The number of Venus expressing neurons was higher in the posterior PVT (pPVT) than in the anterior PVT (aPVT). When OTR-Venus dams were exposed to pups, the number of double-labelled neurons expressing both OTR-Venus and a marker of neuronal activity (c-Fos) was increased in the pPVT compared to non-exposed dams, while the aPVT remained unchanged. To investigate whether OT signaling in the pPVT is essential for maternal behaviors, an OT antagonist (OTA) was transiently or chronically infused into the pPVT of lactating dams during the postpartum period. Although the transient OTR blockade did not affect maternal behaviors, a chronic OTR blockade specifically reduced the duration of crouching behavior over pups. Taken together, these findings suggest that OTR-expressing neurons in the pPVT are involved in maternal crouching behavior.

It\u2019s not what you expect: feedback negativity is independent of reward expectation and affective responsivity in a non-probabilistic task

ERP studies commonly utilize gambling-based reinforcement tasks to elicit feedback negativity (FN) responses. This study used a pattern learning task in order to limit gambling-related fallacious reasoning and possible affective responses to gambling, while investigating relationships between the FN components between high and low reward expectation conditions. Eighteen undergraduates completed measures of reinforcement sensitivity, trait and state affect, and psychophysiological recording. The pattern learning task elicited a FN component for both high and low win expectancy conditions, which was found to be independent of reward expectation and showed little relationship with task and personality variables. We also observed a P3 component, which showed sensitivity to outcome expectancy variation and relationships to measures of anxiety, appetitive motivation, and cortical asymmetry, although these varied by electrode location and expectancy condition. Findings suggest that the FN reflected a binary reward-related signal, with little relationship to reward expectation found in previous studies, in the absence of positive affective responses.

Role of inhibitory processes in relapse prevention treatment

Alcohol dependence is a chronic disorder with frequent relapses during recovery. Most studies have pointed out that craving is the main process involved in relapse, but recently other factors have been implicated in it, such as attentional bias and impulsivity. Some authors consider that different stages could be involved in the relapse process, and each may be governed by different mechanisms: Attentional bias; motivational response to alcohol cues and inhibitory control.Motivationally salient cues attract and hold selective attention, and this “attentional bias, (AB)” is related to individual differences in appetitive and aversive motivation. In a recent review, attentional bias has been shown to be significantly present in alcohol-dependent and is associated with craving and risk to a relapse in alcohol consumption.In alcohol-dependent subjects, alcohol-related cues reach a very high motivational valence (Motivational response, MR), which, in effect, increases craving for alcohol and activates behavioral strategies towards alcohol intake. One method used to assess motivational valence of alcohol is the craving self-assessment. In addition, in recent years, the affective modulation of the startle reflex has been used as an objective measure of craving. It has been shown that subjects with a low baseline startle response when viewing alcohol-associated pictures are at major risk of relapse compared to those with increased reactions.Once alcohol craving has appeared, the subject will either drink or not, depending on his ability to resist his behavior towards alcohol consumption (impulsivity or inhibitory control, IC). Moreover, subjects that exhibit greater impulsivity are those more likely to relapse.Our group has recently conducted a study on a sample of 172 alcohol-dependent patients seen in outpatient therapeutic program during 12 weeks. All of them were assessed with the following measures: Attentional bias was assessed using the dot task, motivational response was evaluated using the affective modulation of the startle reflex paradigm, inhibitory control was assessed by the stop-signal reaction time task. Alcohol relapse variables were: relapse, days to the first relapse and days of accumulated abstinence.One of the most relevant results was that processes related to inhibitory control (Stop-signal reaction time and attentional bias) were the most relevant measures to explain variables related to relapse in alcohol consumption during the treatment period.Our results support the use of assessment strategies, therapeutic and pharmacological inhibtoria aimed at improving the ability of serious alcohol-dependent patients.Disclosure of interestThe author has not supplied his declaration of competing interest.

To eat or not to eat: Effects of food availability on reward system activity during food picture viewing

Neuroimaging studies have started to explore the role of food characteristics (e.g., calorie-content) and psychological factors (e.g., restrained eating, craving) for the human appetitive system, motivated by the significant health implications of food-choice, overeating and overweight/obesity. However, one key aspect of modern food environments, food availability, especially of high energy foods, has not been adequately modeled in experimental research. Food that is immediately available for consumption could elicit stronger reward system activity and associated cognitive control than food that is not currently available for consumption and this could vary as a function of energy density. To examine this question, 32 healthy participants (16 women) underwent functional magnetic resonance imaging while passively viewing available foods – i.e. foods that could be eaten during and after the experiment – and unavailable foods of either high or low-caloric density in a 2 × 2 design. Available compared to unavailable foods elicited higher palatability ratings as well as stronger neural activation in the orbitofrontal cortex (OFC), amygdala, and left caudate nucleus as well as in the anterior cingulate cortex (ACC) – and thus structures implicated in reward and appetitive motivation as well as cognitive control, respectively. Availability effects in the caudate were mainly attributable to the high calorie condition (availability × calorie density interaction). These neuroimaging results support the contention that foods are particularly rewarding when immediately available and particularly so when high in caloric density. Thus, our results are consistent with health promoting interventions utilizing a nudging approach, i.e. aiming at decreasing accessibility of high calorie and increasing accessibility of low calorie foods in daily life. Results also imply that controlling/manipulating food availability may be an important methodological aspect in neuroscientific eating research.

Supplemental Material for Distinct Patterns of Dysfunctional Appetitive and Aversive Motivation in Bipolar Disorder Versus Schizophrenia: An Event-Related Potential Study

Supplemental Material for Distinct Patterns of Dysfunctional Appetitive and Aversive Motivation in Bipolar Disorder Versus Schizophrenia: An Event-Related Potential Study

D-Cycloserine reduces context specificity of sexual extinction learning

Backgroundd-Cycloserine (DCS) enhances extinction processes in animals. Although classical conditioning is hypothesized to play a pivotal role in the aetiology of appetitive motivation problems, no research has been conducted on the effect of DCS on the reduction of context specificity of extinction in human appetitive learning, while facilitation hereof is relevant in the context of treatment of problematic reward-seeking behaviors. MethodsFemale participants were presented with two conditioned stimuli (CSs) that either predicted (CS+) or did not predict (CS−) a potential sexual reward (unconditioned stimulus (US); genital vibrostimulation). Conditioning took place in context A and extinction in context B. Subjects received DCS (125mg) or placebo directly after the experiment on day 1 in a randomized, double-blind, between-subject fashion (Placebo n=31; DCS n=31). Subsequent testing for CS-evoked conditioned responses (CRs) in both the conditioning (A) and the extinction context (B) took place 24h later on day 2. Drug effects on consolidation were then assessed by comparing the recall of sexual extinction memories between the DCS and the placebo groups. ResultsPost learning administration of DCS facilitates sexual extinction memory consolidation and affects extinction’s fundamental context specificity, evidenced by reduced conditioned genital and subjective sexual responses, relative to placebo, for presentations of the reward predicting cue 24h later outside the extinction context. ConclusionsDCS makes appetitive extinction memories context-independent and prevents the return of conditioned response. NMDA receptor glycine site agonists may be potential pharmacotherapies for the prevention of relapse of appetitive motivation disorders with a learned component.

C-27Measures of Executive Functioning and Appetitive Motivation Predict Gender-Specific Cognitive versus Gambling Task Choices

C-27Measures of Executive Functioning and Appetitive Motivation Predict Gender-Specific Cognitive versus Gambling Task Choices

Low Dopamine D2 Receptor Increases Vulnerability to Obesity Via Reduced Physical Activity, Not Increased Appetitive Motivation

BackgroundThe dopamine D2 receptor (D2R) has received much attention in obesity studies. Data indicate that D2R is reduced in obesity and that the TaqA1 D2R variant may be more prevalent among obese persons. It is often suggested that reduced D2R generates a reward deficiency and altered appetitive motivation that induces compulsive eating and contributes to obesity. Although dopamine is known to regulate physical activity, it is often neglected in these studies, leaving open the question of whether reduced D2R contributes to obesity through alterations in energy expenditure and activity. MethodsWe generated a D2R knockdown (KD) mouse line and assessed both energy expenditure and appetitive motivation under conditions of diet-induced obesity. ResultsThe KD mice did not gain more weight or show increased appetitive motivation compared with wild-type mice in a standard environment; however, in an enriched environment with voluntary exercise opportunities, KD mice exhibited dramatically lower activity and became more obese than wild-type mice, obtaining no protective benefit from exercise opportunities. ConclusionsThese data suggest the primary contribution of altered D2R signaling to obesity lies in altered energy expenditure rather than the induction of compulsive overeating.

Effects of two cognitive regulation strategies on the processing of food cues in high restrained eaters. An event-related potential study

This study tested the effects of cognitive regulation (CR) on the attentional processing of food cues in restrained eaters (RE) by means of event-related potentials (ERPs). In a within-subject-design, RE (n = 23) were presented pictures of highly palatable food and office items while ERPs were recorded. Prior to the presentation of the food stimuli, participants were either instructed to engage in reappraisal or to attempt to suppress cravings – both cognitive regulation (CR) strategies – or to simply watch the pictures. Prior to the presentation of the neutral stimuli, participants were instructed to simply watch them. Following each picture presentation, momentary craving was assessed. Main results showed that engaging in CR significantly reduced ERP amplitudes compared to the food watch condition. Passively attending to food pictures yielded significantly higher craving scores compared to engaging in CR. In addition, craving was significantly lower in the reappraisal than in the suppression condition. Therefore, reappraisal could potentially increase the ability to inhibit the appetitive motivation to eat.

Sex Differences and the Impact of Chronic Stress and Recovery on Instrumental Learning.

We have previously shown that 21-day chronic restraint stress impacts instrumental learning, but overall few studies have examined sex differences on the impact of stress on learning. We further examined sex differences in response to extended 42-day chronic stress on instrumental learning, as well as recovery from chronic stress. Rats were tested in aversive training tasks with or without prior appetitive experience, and daily body weight data was collected as an index of stress. Relative to control animals, reduced body weight was maintained from day 22 through day 42 across the stress period for males, but not for females. Stressed males had increased response speed and lower learning efficiency during appetitive acquisition and aversive learning. Males overall showed slower escape shaping times and more shock exposure. In contrast, stressed females showed slower appetitive response speeds and higher appetitive and aversive efficiency but overall reduced avoidance rates during acquisition and maintenance for transfer animals and during maintenance for aversive-only animals. These tasks reveal important nuances on the effect of stress on goal-directed behavior and further highlight sexually divergent effects on appetitive versus aversive motivation. Furthermore, these data underscore that systems are temporally impacted by chronic stress in a sexually divergent pattern.

Diminished appetitive startle modulation following targeted inhibition of prefrontal cortex.

From an evolutionary perspective the startle eye-blink response forms an integral part of the human avoidance behavioral repertoire and is typically diminished by pleasant emotional states. In major depressive disorder (MDD) appetitive motivation is impaired, evident in a reduced interference of positive emotion with the startle response. Given the pivotal role of frontostriatal neurocircuitry in orchestrating appetitive motivation, we hypothesized that inhibitory transcranial magnetic stimulation (TMS) would reduce appetitive neuromodulation in a manner similar to MDD. Based on a pre-TMS functional MRI (fMRI) experiment we selected the left dorsolateral and dorsomedial prefrontal cortices as target regions for subsequent sham-controlled inhibitory theta-burst TMS (TBS) in 40 healthy male volunteers. Consistent with our hypothesis, between-group comparisons revealed a TBS-induced inhibition of appetitive neuromodulation, manifest in a diminished startle response suppression by hedonic stimuli. Collectively, our results suggest that functional integrity of left dorsolateral and dorsomedial prefrontal cortex is critical for mediating a pleasure-induced down-regulation of avoidance responses which may protect the brain from a depressogenic preponderance of defensive stress.

Valuation and Cognitive Circuitry in Anorexia Nervosa: Disentangling Appetite from the Effort to Obtain a Reward

Motivation is classically defined as the amount of effort one is willing to expend to acquire a reward. In humans, rewards may range from basic or primary (e.g., drugs of abuse, sex, money, palatable food) to more complex, personal ones (e.g., social engagement or reciprocity, entertainment, hobbies), and working toward those rewards, whether immediate or distant, often guides the choices we make daily. Findings in healthy populations have identified key neural regions involved in anticipation, evaluation, and decision making during reward processing and demonstrated the impact of internal states modulating these, including stress (1) and sleep (2), among others. Disruption in these circuits underlies the pathophysiology of several neuropsychiatric conditions (i.e., addiction to substances, sex, and gambling; eating disorders; major depression and anxiety; autism). Of these conditions, anorexia nervosa (AN), marked by a refusal to consume adequate nutrients in a state of severe starvation, is one of the most difficult to treat and deadly (3). This fact owes largely to the necessity of the primary reward in question (food) to sustain health and, ultimately, life. Mounting evidence of neurohormonal dysfunction contributes to aberrant food reward and appetite in AN, but there is little clinical application of these findings to treatment. A study by Wierenga et al. (4) in this issue of Biological Psychiatry may have implications for enhancing efficacy of treatment for AN. Their study focuses on the impact of internal appetitive drive on brain activity during decision making for monetary cues in women remitted from AN (RAN) compared with healthy control (HC) women. This clever and wellformulated design sidesteps numerous potential confounders in identifying brain activity deficits in AN. In particular, rather than food cues, the authors used a robust delay discounting paradigm to assess immediate versus future valuation of monetary rewards; this design avoids the use of stimuli which commonly elicits anxiety in this population. The task simultaneously evokes neural response to reward and cognitive control, both of which are abnormal in AN. In a group of subjects (23 RAN women, 17 HC women) who were carefully phenotyped and medication-free, one of the novel features of the design was the counterbalanced task administration across two states of appetitive motivation: hunger (after 16-hour fast) and satiety (meal consumption 2 hours before the scan). The authors showed enhanced activity to immediate rewards in valuation circuitry (ventral striatum, dorsal caudate, anterior cingulate cortex) during hunger in HC women compared with satiety but no differences across appetitive states in RAN women, who tended to show hyperactivity in these regions during satiation compared with HC women. The opposite trend emerged in HC women during decision making, with

Dissociable roles for the basolateral amygdala and orbitofrontal cortex in decision-making under risk of punishment.

Several neuropsychiatric disorders are associated with abnormal decision-making involving risk of punishment, but the neural basis of this association remains poorly understood. Altered activity in brain systems including the basolateral amygdala (BLA) and orbitofrontal cortex (OFC) can accompany these same disorders, and these structures are implicated in some forms of decision-making. The current study investigated the role of the BLA and OFC in decision-making under risk of explicit punishment. Rats were trained in the risky decision-making task (RDT), in which they chose between two levers, one that delivered a small safe reward, and the other that delivered a large reward accompanied by varying risks of footshock punishment. Following training, they received sham or neurotoxic lesions of BLA or OFC, followed by RDT retesting. BLA lesions increased choice of the large risky reward (greater risk-taking) compared to both prelesion performance and sham controls. When reward magnitudes were equated, both BLA lesion and control groups shifted their choice to the safe (no shock) reward lever, indicating that the lesions did not impair punishment sensitivity. In contrast to BLA lesions, OFC lesions significantly decreased risk-taking compared with sham controls, but did not impair discrimination between different reward magnitudes or alter baseline levels of anxiety. Finally, neither lesion significantly affected food-motivated lever pressing under various fixed ratio schedules, indicating that lesion-induced alterations in risk-taking were not secondary to changes in appetitive motivation. Together, these findings indicate distinct roles for the BLA and OFC in decision-making under risk of explicit punishment.

Broadening the definition of resilience and "reappraising" the use of appetitive motivation.

Kalisch et al.'s PASTOR model synthesizes current knowledge of resilience, focusing on mechanisms as a common pathway to outcomes and highlighting neuroscience as a method for exploring this. We propose the model broaden its definition of resiliency to include positive indices of recovery, include positive affect as a mechanism, and approach motivation as distinct from overcoming aversive motivation.

Please keep calm: investigating hippocampal function without stress.

Please keep calm: investigating hippocampal function without stress.

Effects of long-term meditation practice on attentional biases towards emotional faces: An eye-tracking study

Attentional biases towards affective stimuli reflect an individual balance of appetitive and aversive motivational systems. Vigilance in relation to threatening information reflects emotional imbalance, associated with affective and somatic problems. It is known that meditation practice significantly improves control of attention, which is considered to be a tool for adaptive emotional regulation. In this regard, the main aim of the present study was to evaluate the influence of meditation on attentional bias towards neutral and emotional facial expressions. Eyes were tracked while 21 healthy controls and 23 experienced meditators (all males) viewed displays consisting of four facial expressions (neutral, angry, fearful and happy) for 10 s. Measures of biases in initial orienting and maintenance of attention were assessed. No effects were found for initial orienting biases. Meditators spent significantly less time viewing angry and fearful faces than control subjects. Furthermore, meditators selectively attended to happy faces whereas control subjects showed attentional biases towards both angry and happy faces. In sum we can conclude that long-term meditation practice adaptively affects attentional biases towards motivationally significant stimuli and that these biases reflect positive mood and predominance of appetitive motivation.

Amylin receptor signaling in the nucleus accumbens negatively modulates μ-opioid-driven feeding.

Amylin is a peptide co-secreted with insulin that penetrates into the brain, and produces satiation-like effects via actions in the brainstem, hypothalamus, and mesencephalon. Little is known, however, about the effects of amylin in the nucleus accumbens shell (AcbSh), where a circumscribed zone of intense amylin receptor (AMY-R) binding overlaps reported mappings of a 'hotspot' for μ-opioid receptor (μ-OR) amplification of food reward. Here, the ability of intra-AcbSh AMY-R signaling to modulate μ-OR-driven feeding was explored. Amylin (1-30 ng) was administered with the μ-OR agonist, D-Ala2, N-MePhe4, Gly-ol]-enkephalin (DAMGO) (0.25 μg), directly into the AcbSh of ad libitum-maintained rats. Amylin dose-dependently reversed DAMGO-induced hyperphagia; 3 ng of amylin reduced DAMGO-mediated feeding by nearly 50%. This dose was, however, completely ineffective at altering DAMGO-induced feeding in the anterior dorsal striatum. Intra-AcbSh amylin alone (3-30 ng) modestly suppressed 10% sucrose intake in ad libitum-maintained rats, and chow in food-deprived rats, but only at the 30-ng dose. This result indicates that reversal of AcbSh DAMGO-induced feeding at a 10-fold lower dose was neither due to malaise nor motoric impairment. Finally, intra-AcbSh infusion of the AMY-R antagonist, AC187 (20 μg), significantly attenuated the ability of prefeeding to suppress DAMGO-induced food intake, with no effects in non-prefed rats. Hence, AMY-R signaling negatively modulates μ-OR-mediated appetitive responses at the level of the AcbSh. The results with AC187 indicate that endogenous AMY-R transmission in the AcbSh curtails opioid function in the postprandial period, suggesting a novel pathway for peripheral-central integration in the control of appetitive motivation and opioid reward.

Dopamine and the Cognitive Downside of a Promised Bonus

It is often assumed that the promise of a monetary bonus improves cognitive control. We show that in fact appetitive motivation can also impair cognitive control, depending on baseline levels of dopamine-synthesis capacity in the striatum. These data not only demonstrate that appetitive motivation can have paradoxical detrimental effects for cognitive control but also provide a mechanistic account of these effects.