The Contribution of the Amygdala to Reward-Related Learning and Extinction

There has been substantial research into the role of the amygdala in fear conditioning and extinction of conditioned fear. The role of the amygdala in appetitive conditioning is relatively less explored. Here, we will review research into the role of the amygdala in reward‐related learning. Research to date suggests that the basolateral and central amygdala are responsible for learning about distinct aspects of a reinforcing event. For example, the basolateral amygdala is essential for distinguishing and choosing between specific rewards based on the specific‐sensory properties of those rewards as well as updating the relative value of specific rewarding events. In contrast, the central amygdala is involved in encoding reinforcement more generally and for regulating motivational influences on responding. We will also review what is known about the role of the amygdala in extinction of reward‐related behaviours and highlight areas for future research

Relating goal-directed behaviour to grazing in persons with obesity with and without eating disorder features

Background: Both obesity and eating disorders (ED) have been associated with reductions in purposeful, flexible goal-directed behaviour, and with an overreliance on more rigid habitual behaviour. It is currently unknown whether grazing, an eating style which is common in both conditions, is related to goal-directed behaviour. The current study therefore aimed to relate grazing to goal-directed behaviour in a group of participants with obesity with and without ED features, compared to a healthy-weight control group. Methods: Participants (N = 87; 67.8% women, mean age 28.57 years), of whom 19 had obesity and significant eating disorder features, 25 had obesity but without marked eating disorder features, and 43 were age- and sex-matched healthy-weight controls, completed two instrumental learning tasks assessing action-outcome contingency sensitivity and devaluation sensitivity, as well as demographic and eating disorder-related questionnaires. Gamma and Ordinary Least Squares regressions were performed to examine the effect of group and grazing on goal-directed behaviour. Results: Lower action-outcome contingency sensitivity was found in the group with obesity and with eating disorder features than in the group with obesity but without eating disorder features or in healthy controls. No group differences in devaluation sensitivity were found. A small but significant relationship was found between grazing severity and contingency sensitivity in the group with obesity and eating disorder features, such that increasing grazing severity was associated with less diminished contingency sensitivity. Conclusions: There is some indication that in persons with obesity and eating disorder features instrumental behaviour is less flexible and adaptive; furthermore, within this group grazing may represent a goal-directed behaviour, despite unhelpful long-term implications of grazing

Corticostriatal circuitry and habitual ethanol seeking

The development of alcohol-use disorders is thought to involve a transition from casual alcohol use to uncontrolled alcohol-seeking behavior. This review will highlight evidence suggesting that the shift toward inflexible alcohol seeking that occurs across the development of addiction consists, in part, of a progression from goal-directed to habitual behaviors. This shift in “response strategy” is thought to be largely regulated by corticostriatal network activity. Indeed, specific neuroanatomical substrates within the prefrontal cortex and the striatum have been identified as playing opposing roles in the expression of actions and habits. A majority of the research on the neurobiology of habitual behavior has focused on non-drug reward seeking. Here, we will highlight recent research identifying corticostriatal structures that regulate the expression of habitual alcohol seeking and a comparison will be made when possible to findings for non-drug rewards

Changes in the influence of alcohol-paired stimuli on alcohol seeking across extended training.

Previous work has demonstrated that goal-directed control of alcohol seeking and other drug-related behaviors is reduced following extended self-administration and drug exposure. Here we examined how the magnitude of stimulus influences on responding changes across similar training and drug exposure. Rats self-administered alcohol or sucrose for two or eight weeks. Previous work has shown that eight, but not two weeks of self-administration produces habitual alcohol seeking. Next, all animals received equivalent Pavlovian conditioning sessions where a discrete stimulus predicted the delivery of alcohol or sucrose. Finally, the impact of the stimuli on ongoing instrumental responding was examined in a Pavlovian-instrumental transfer (PIT) test. While a significant PIT effect was observed following two weeks of either alcohol or sucrose self-administration, the magnitude of this effect was greater following eight weeks of training. The specificity of the PIT effect appeared unchanged by extended training. While it is well established that evaluation of the outcome of responding contributes less to behavioral control following extended training and/or drug exposure, our data indicate that reward-predictive stimuli have a stronger contribution to responding after extended training. Together, these findings provide insight into the factors that control behavior after extended drug use which will be important for developing effective methods for controlling and ideally reducing these behaviors

Noradrenergic β-receptor antagonism in the basolateral amygdala impairs reconsolidation, but not extinction, of alcohol self-administration : intra-BLA propranolol impairs reconsolidation of alcohol self-administration

A critical barrier to recovery from alcohol addiction is relapse propensity. Alcohol cues can trigger relapse, and pharmacologically facilitating processes such as extinction, which decreases cue associations, may help prevent relapse. The noradrenergic system mediates extinction learning for alcohol; however, the neural locus of this effect is unknown. This study sought to determine whether the basolateral amygdala (BLA), a region critical for fear extinction, also mediates extinction of alcohol seeking. Hooded Wistar rats (N = 12-15 per experiment) were implanted with bilateral cannula targeting the BLA and trained to lever press for 10% ethanol during auditory or visual cues. Infusions of the beta-receptor antagonist propranolol (2 mu g/side) were administered prior to extinction (Experiment 1), and rats assessed for relapse-like behaviour two weeks later, thus allowing for spontaneous recovery. We expected intra-BLA propranolol to impair extinction learning; however, propranololtreated rats exhibited reduced responding in the test of spontaneous recovery, suggesting enhanced extinction. We investigated this unexpected result by determining if propranolol treatment affected memory processes other than extinction. In a subsequent experiment, rats were infused with propranolol immediately after extinction to target consolidation of extinction (Experiment 2a), and assessed for spontaneous recovery. Propranolol was also infused after self-administration to target reconsolidation of the original learning (Experiment 2b). Propranolol treatment had no effect on consolidation of extinction learning, but impaired reconsolidation of self-administration. Propranolol administered prior to a self-administration session did not affect reinforced responding (Experiment 2c). Extinction and reconsolidation are opposing processes triggered by specific test conditions. We suggest our test conditions induced reconsolidation of self-administration memory by propranolol, rather than modulation of extinction. Thus, our data implicates infra-BLA noradrenergic beta-receptors in reconsolidation of alcohol self-administration memory

Recent developments in the behavioural and pharmacological enhancement of extinction of drug seeking

One of the principal barriers to overcoming addiction is the propensity to relapse, even after months or years of abstinence. Relapse can be precipitated by cues and contexts associated with drug use; thus, decreasing the conditioned properties of these cues and contexts may assist in preventing relapse. The predictive power of drug cues and contexts can be reduced by repeatedly presenting them in the absence of the drug reinforcer, a process known as extinction. The potential of extinction to limit relapse has generated considerable interest and research over the past few decades. While pre-clinical animal models suggest extinction learning assists relapse prevention, treatment efficacy is often lacking when extinction learning principles are translated into clinical trials. Conklin and Tiffany (Addiction, 2002) suggest the lack of efficacy in clinical practice may be due to limited translation of procedures demonstrated through animal research and propose several methodological improvements to enhance extinction learning for drug addiction. This review will examine recent advances in the behavioural and pharmacological manipulation of extinction learning, based on research from pre-clinical models. In addition, the translation of pre-clinical findings—both those suggested by Conklin and Tiffany (2002) and novel demonstrations from the past 13 years—into clinical trials and the efficacy of these methods in reducing craving and relapse, where available, will be discussed. Finally, we highlight areas where promising pre-clinical models have not yet been integrated into current clinical practice but, if applied, could improve upon existing behavioural and pharmacological methods

Optogenetic stimulation of the locus coeruleus enhances appetitive extinction in rats

Extinction is a specific example of learning where a previously reinforced stimulus or response is no longer reinforced, and the previously learned behaviour is no longer necessary and must be modified. Current theories suggest extinction is not the erasure of the original learning but involves new learning that acts to suppress the original behaviour. Evidence for this can be found when the original behaviour recovers following the passage of time (spontaneous recovery) or reintroduction of the reinforcement (i.e. reinstatement). Recent studies have shown that pharmacological manipulation of noradrenaline (NA) or its receptors can influence appetitive extinction; however, the role and source of endogenous NA in these effects are unknown. Here, we examined the role of the locus coeruleus (LC) in appetitive extinction. Specifically, we tested whether optogenetic stimulation of LC neurons during extinction of a food-seeking behaviour would enhance extinction evidenced by reduced spontaneous recovery in future tests. LC stimulation during extinction trials did not change the rate of extinction but did serve to reduce subsequent spontaneous recovery, suggesting that stimulation of the LC can augment reward-related extinction. Optogenetic inhibition of the LC during extinction trials reduced responding during the trials where it was applied, but no long-lasting changes in the retention of extinction were observed. Since not all LC cells expressed halorhodopsin, it is possible that more complete LC inhibition or pathway-specific targeting would be more effective at suppressing extinction learning. These results provide further insight into the neural basis of appetitive extinction, and in particular the role of the LC. A deeper understanding of the physiological bases of extinction can aid development of more effective extinction-based therapies

Grazing in adults with obesity and eating disorders : a systematic review of associated clinical features and meta-analysis of prevalence

Grazing, the unstructured, repetitive eating of small amounts of food, is a pattern of eating which has been associated with negative outcomes following bariatric surgery. Less is known about grazing in eating disorders and in non-surgical obese samples. This review aims to critically examine the existing research on the prevalence of grazing, associated treatment outcomes, and clinical correlates in adults with eating disorders and/or obesity, in clinical and community settings. A systematic electronic database search yielded 38 studies which met inclusion criteria for the review. A meta-analysis was conducted using prevalence data from 32 studies (31 datasets). Mean pooled prevalence in obesity (n = 26 studies) was 33.20% (95% CI [27.54, 39.11]) at pre-weight loss treatment, 28.16% (95% CI [17.86, 39.73]) at follow-up, and 23.32% (95% CI [3.07, 52.04]) in the community. Nine studies provided prevalence estimates in eating disorders: 58.25% (95% CI [52.75, 63.66]) in bulimia nervosa; 67.77% (95% CI [44.96, 87.13]) in binge eating disorder; and 34.31% (95% CI [26.56, 42.49]) in anorexia nervosa. The results suggest that grazing is widely prevalent within obesity and eating disorders. There is mixed evidence to suggest that grazing (especially a "compulsive" subtype including a sense of loss of control) is associated with poorer weight loss treatment outcomes in obesity, lower mood, increased eating disorder symptomatology, and decreased mental health-related quality of life. Differences in the operationalisation of grazing may account for inconsistent findings in regards to specific correlates and risks associated with this behaviour; therefore, there is an urgent need to refine and adopt a consistent definition of grazing