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The relative inability to produce effortful movements is the most specific motor sign of Parkinson's disease, which is primarily characterized by loss of dopaminergic terminals in the putamen. The motor motivation hypothesis suggests that this motor deficit may not reflect a deficiency in motor control per se , but a deficiency in cost-benefit considerations for motor effort. For the first time, we investigated the quantitative effect of dopamine depletion on the motivation of motor effort in Parkinson's disease. A total of 21 early-stage, unmedicated patients with Parkinson's disease and 26 healthy controls were included. An incentivized force task was used to capture the amount of effort participants were willing to invest for different monetary incentive levels and dopamine transporter depletion in the bilateral putamen was assessed. Our results demonstrate that patients with Parkinson's disease applied significantly less grip force than healthy controls, especially for low incentive levels. Congruously, decrease of motor effort with greater loss of putaminal dopaminergic terminals was most pronounced for low incentive levels. This signifies that putaminal dopamine is most critical to motor effort when the trade-off with the benefit is poor. Taken together, we provide direct evidence that the reduction of effortful movements in Parkinson's disease depends on motivation and that this effect is associated with putaminal dopaminergic degeneration. [ABSTRACT FROM AUTHOR]

In our modern environment, we are bombarded with stimuli or cues that exert significant influence over our actions. The extent to which such cues attain control over or disrupt goal-directed behavior is dependent on several factors, including one's inherent tendencies. Using a rodent model, we have shown that individuals vary in the value they place on stimuli associated with reward. Some individuals, termed "goal-trackers," primarily attribute predictive value to reward cues, whereas others, termed "sign-trackers," attribute predictive and incentive value. Thus, for sign-trackers, the reward cue is transformed into an incentive stimulus that is capable of eliciting maladaptive behaviors. The sign-tracker/goal-tracker animal model has allowed us to refine our understanding of behavioral and computational theories related to reward learning and to parse the underlying neural processes. Further, the neurobehavioral profile of sign-trackers is relevant to several psychiatric disorders, including substance use disorder, impulse control disorders, obsessive–compulsive disorder, attention-deficit/hyperactivity disorder, and posttraumatic stress disorder. This model, therefore, can advance our understanding of the psychological and neurobiological mechanisms that contribute to individual differences in vulnerability to psychopathology. Notably, initial attempts at translation—capturing individual variability in the propensity to sign-track in humans—have been promising and in line with what we have learned from the animal model. In this review, we highlight the pivotal role played by the sign-tracker/goal-tracker animal model in enriching our understanding of the psychological and neural basis of motivated behavior and psychiatric symptomatology. [ABSTRACT FROM AUTHOR]

Background: Substance use disorders (SUDs) are heterogeneous across multiple functional domains. Various frameworks posit that domains (e.g., executive function) contribute to the persistence of SUDs; however, the domains identified in different studies vary. Objectives: We used factor analysis to identify the underlying latent domains present in a large sample (N = 5,244, 55.8% male) with a variety of SUDs to yield findings more generalizable than studies with a narrower focus. Method: Participants (1,384 controls and 3,860 participants with one or more SUDs including alcohol, cocaine, cannabis, and/or opioid use disorders) completed the Semi-Structured Assessment for Drug Dependence and Alcoholism, the NEO Personality Inventory, and the Wisconsin Card Sorting Test. Exploratory factor analysis (EFA) and fit indices (root mean-squared error of approximation (RMSEA), Comparative Fit Index (CFI), and Tucker-Lewis Index (TLI)) were used to examine different latent variable models. A multiple indicators, multiple causes (MIMIC) approach-tested associations of the latent variables with sociodemographics, substance use, and a history of abuse/neglect. Results: A six-factor model (predominant alcohol, predominant cocaine, predominant opioid, externalizing, personality, and executive function) provided the best fit [RMSEA = 0.063 (90% CI 0.060, 0.066), CFI = 0.98, TLI = 0.96]. All factors were moderately correlated (coefficient = 0.25–0.55, p <.05) with the exception of executive function. MIMIC analysis revealed different patterns of associations (all p <.0001) with sociodemographics, substance use, and a history of abuse/neglect among the factors. Conclusions: The domains identified, particularly executive function, were parallel to those observed previously. These factors underscore the heterogeneous nature of SUDs and may be useful in developing more targeted clinical interventions. [ABSTRACT FROM AUTHOR]

Synthetic exendin-4 (EX4, exenatide), is a GLP-1 receptor agonist used clinically to treat glycemia in Type-2 diabetes mellitus. EX4 also promotes weight loss and alters food reward-seeking behaviors in part due to activation of GLP-1 receptors in the mesolimbic dopamine system. Evidence suggests that GLP-1 receptor activity can directly attenuate cue-induced reward seeking. Here, we tested the effects of EX4 (0.6, 1.2, and 2.4 μg/kg, i.p.) on incentive cue (IC) responding, using a task where rats emit a nosepoke response during an intermittent reward-predictive IC to obtain a sucrose reward. EX4 dose-dependently attenuated responding to ICs and increased the latencies to respond to the IC and enter the sucrose reward cup. Moreover, EX4 dose-dependently decreased the total number of active port nosepokes for every cue presented. There was no effect of EX4 on the number of reward cup entries per reward earned, a related reward-seeking metric with similar locomotor demand. There was a dose-dependent interaction between the EX4 dose and session time on the responding to ICs and nosepoke response latency. The interaction indicated that effects of EX4 at the beginning and end of the session differed by the dose of EX4, suggesting dose-dependent pharmacokinetic effects. EX4 had no effect on free sucrose consumption behavior (i.e., total volume consumed, bout size, number of bouts) within the range of total sucrose volumes obtainable during the IC task (~3.5 ml). However, when rats were given unrestricted access for 1 h, where rats obtained much larger total volumes of sucrose (~30 ml), we observed some dose-dependent EX4 effects on drinking behavior, including decreases in total volume consumed. Together, these findings suggest that activation of the GLP-1 receptor modulates the incentive properties of cues attributed with motivational significance. [ABSTRACT FROM AUTHOR]

Rationale: Relapse into substance use is often triggered by exposure to drug-related environmental cues. The magnitude of drug seeking depends on the duration of abstinence, a phenomenon known as the incubation of drug craving. Clinical and preclinical research shows that the insular cortex is involved in substance use disorders and cue-induced drug seeking. However, the role of the insula on memory retrieval and motivational integration for cue-elicited drug seeking remains to be determined. Objectives: We investigated the role of the anterior insular cortex (aIC) and its glutamatergic projection to amygdala nuclei (aIC-AMY) on the expression of conditioned place preference (CPP) during early and late abstinence. Methods: Male adult C57BL/6J mice underwent amphetamine-induced CPP, and their preference was tested following 1 or 14 days of abstinence. aIC and aIC-AMY functional role in CPP expression was assessed at both abstinence periods by employing optogenetic silencing and behavioral pharmacology. Results: Compared to a single day, an exacerbated preference for the amphetamine-paired context was observed after 14 days of abstinence. Photoinhibition of either aIC or aIC-AMY projection reduced CPP expression following late but not early abstinence. Similarly, the antagonism of aIC NMDA receptors reduced CPP expression after 14 days of abstinence but not 1 day. Conclusions: These results suggest that aIC and its glutamatergic output to amygdala nuclei constitute critical neurobiological substrates mediating enhanced motivational cue reactivity during the incubation of amphetamine craving rather than contextual memory recall. Moreover, cortical NMDA receptor signaling may become sensitized during abstinence, ultimately modulating disproportioned drug seeking. [ABSTRACT FROM AUTHOR]

Creativity often entails gaining a novel perspective, yet it remains uncertain how this is accomplished. Atypical salience processing may foster creative thinking by prioritizing putatively irrelevant information, thereby broadening the material accessible for idea generation and inhibiting attentional fixedness; in essence, motivating creative individuals to incorporate information that others overlook. [ABSTRACT FROM AUTHOR]

Synthetic exendin-4 (EX4, exenatide), is a GLP-1 receptor agonist used clinically to treat glycemia in Type-2 diabetes mellitus. EX4 also promotes weight loss and alters food reward-seeking behaviors in part due to activation of GLP-1 receptors in the mesolimbic dopamine system. Evidence suggests that GLP-1 receptor activity can directly attenuate cue-induced reward seeking. Here, we tested the effects of EX4 (0.6, 1.2, and 2.4 μg/kg, i.p.) on incentive cue (IC) responding, using a task where rats emit a nosepoke response during an intermittent reward-predictive IC to obtain a sucrose reward. EX4 dose-dependently attenuated responding to ICs and increased the latencies to respond to the IC and enter the sucrose reward cup. Moreover, EX4 dose-dependently decreased the total number of active port nosepokes for every cue presented. There was no effect of EX4 on the number of reward cup entries per reward earned, a related reward-seeking metric with similar locomotor demand. There was a dose-dependent interaction between the EX4 dose and session time on the responding to ICs and nosepoke response latency. The interaction indicated that effects of EX4 at the beginning and end of the session differed by the dose of EX4, suggesting dose-dependent pharmacokinetic effects. EX4 had no effect on free sucrose consumption behavior (i.e., total volume consumed, bout size, number of bouts) within the range of total sucrose volumes obtainable during the IC task (~3.5 ml). However, when rats were given unrestricted access for 1 h, where rats obtained much larger total volumes of sucrose (~30 ml), we observed some dose-dependent EX4 effects on drinking behavior, including decreases in total volume consumed. Together, these findings suggest that activation of the GLP-1 receptor modulates the incentive properties of cues attributed with motivational significance.

Motivationally salient stimuli, such as those associated with reward, can automatically gain attentional prioritisation – even when individuals are motivated to ignore such stimuli. This 'attentional bias for reward' has often been interpreted as evidence for involuntary Pavlovian 'sign tracking' behaviour. The prioritisation of reward-signalling distractors may additionally reflect a drive to gain information about the state of the world, irrespective of the particular reward that is being signalled. In the current study we assessed whether forewarning participants on each trial as to the upcoming features of a distractor would reduce reward-related attentional capture. This manipulation reduces the information provided by the distractor, without affecting the magnitude of the signalled reward. Using eye tracking in Experiment 1, we found that reward-related attentional capture was virtually eliminated when participants were informed of the upcoming distractor colour (relative to the baseline condition when no information was provided). In Experiment 2, using a response-time version of the task, we again found a significant reduction in reward-related attentional capture when participants received information about the colour of an upcoming distractor, or information about the value of the upcoming reward. Finally, in Experiment 3 we assessed whether participants were using the pre-trial information to strategically inhibit attention to the upcoming distractor colour. The results of these experiments are discussed within the context of information-seeking accounts of reward-related attentional capture effects. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIMS: Compulsive Sexual Behavior Disorder (CSBD) is characterized by increased reactivity to erotic reward cues. Cue-encoded reward parameters, such as type (e.g. erotic or monetary) or probability of anticipated reward, shape reward-related motivational processes, increase the attractiveness of cues and therefore might enhance maladaptive behavioral patterns in CSBD. Studies on the neural patterns of cue processing in individuals with CSBD have been limited mainly to ventral striatal responses. Therefore, here we aimed to examine the cue reactivity of multiple key structures in the brains reward system, taking into account not only the type of predicted reward but also its probability. METHODS: Twenty Nine men seeking professional help due to CSBD and 24 healthy volunteers took part in an fMRI study with a modified Incentive Delay Task with erotic and monetary rewards preceded by cues indicating a 25%, 50%, or 75% chance of reward. Analyses of functional patterns of activity related to cue type and probability were conducted on the whole-brain and ROI levels. RESULTS: Increased anticipatory response to cues predictive of erotic rewards was observed among CSBD participants when compared to controls, in the ventral striatum and anterior orbitofrontal cortex (aOFC). The activity in aOFC was modulated by reward probability. DISCUSSION AND CONCLUSIONS: Type of anticipated reward (erotic vs monetary) affects reward-related behavioral motivation in CSBD more strongly than reward probability. We present evidence of abnormal aOFC function in CSBD by demonstrating the recruitment of additional subsections of this region by erotic reward cues.

It is estimated that nearly a third of people who abuse drugs started with prescription opioid medicines. Approximately, 11.5 million Americans used prescription drugs recreationally in 2016, and in 2018, 46,802 Americans died as the result of an opioid overdose, including prescription opioids, heroin, and illicitly manufactured fentanyl (National Institutes on Drug Abuse (2020) Opioid Overdose Crisis. https://www.drugabuse.gov/drugs-abuse/opioids/opioid-overdose-crisis . Accessed 06 June 2020). Yet physicians will continue to prescribe oral opioids for moderate-to-severe pain in the absence of alternative therapeutics, underscoring the importance in understanding how drug choice can influence detrimental outcomes. One of the opioid prescription medications that led to this crisis is oxycodone, where misuse of this drug has been rampant. Being one of the most highly prescribed opioid medications for treating moderate-to-severe pain as reflected in the skyrocketed increase in retail sales of 866% between 1997 and 2007, oxycodone was initially suggested to be less addictive than morphine. The false-claimed non-addictive formulation of oxycodone, OxyContin, further contributed to the opioid crisis. Abuse was often carried out by crushing the pills for immediate burst release, typically by nasal insufflation, or by liquefying the pills for intravenous injection. Here, we review oxycodone pharmacology and abuse liability as well as present the hypothesis that oxycodone may exhibit a unique pharmacology that contributes to its high likability and abuse susceptibility. We will discuss various mechanisms that likely contribute to the high abuse rate of oxycodone including clinical drug likability, pharmacokinetics, pharmacodynamics, differences in its actions within mesolimbic reward circuity compared to other opioids, and the possibility of differential molecular and cellular receptor interactions that contribute to its selective effects. We will also discuss marketing strategies and drug difference that likely contributes to the oxycodone opioid use disorders and addiction.

Background: Brain-based interventions are needed to address persistent relapse in alcohol use disorder (AUD). Neuroimaging evidence suggests higher frontal connectivity as well as higher within-network connectivity of theoretically defined addiction networks are associated with reduced relapse rates and extended abstinence during follow-up periods. Objective: /Hypothesis: A longitudinal randomized double-blind sham-controlled clinical trial investigated whether a non-invasive neuromodulation intervention delivered during early abstinence can (i) modulate connectivity of addiction networks supporting abstinence and (ii) improve relapse rates. Hypotheses: Active transcranial direct current stimulation (tDCS) will (i) increase connectivity of addiction networks known to support abstinence and (ii) reduce relapse rates. Methods: Short-term abstinent AUD participants (n = 60) were assigned to 5 days of either active tDCS or sham during cognitive training. Causal discovery analysis (CDA) examined the directional influence from left dorsolateral prefrontal cortex (LDLPFC, stimulation site) to addiction networks that support abstinence. Results: Active tDCS had an effect on the average strength of CDA-determined connectivity from LDLPFC to the incentive salience and negative emotionality addiction networks - increasing in the active tDCS group only. Active tDCS had an effect on relapse rates following the intervention, with lower probability of relapse in the active tDCS vs. sham. Active tDCS showed an unexpected sex-dependent effect on relapse rates. Conclusion: Our results suggest that LDLPFC stimulation delivered during early abstinence has an effect on addiction networks supporting abstinence and on relapse rates. The unexpected sex-dependent neuromodulation effects need to be further examined in larger clinical trials.

The survival of an organism is dependent on its ability to respond to cues in the environment. Such cues can attain control over behavior as a function of the value ascribed to them. Some individuals have an inherent tendency to attribute reward-paired cues with incentive motivational value, or incentive salience. For these individuals, termed sign-trackers, a discrete cue that precedes reward delivery becomes attractive and desirable in its own right. Prior work suggests that the behavior of sign-trackers is dopamine-dependent, and cue-elicited dopamine in the NAc is believed to encode the incentive value of reward cues. Here we exploited the temporal resolution of optogenetics to determine whether selective inhibition of ventral tegmental area (VTA) dopamine neurons during cue presentation attenuates the propensity to sign-track. Using male tyrosine hydroxylase (TH)-Cre Long Evans rats, it was found that, under baseline conditions, ~84% of TH-Cre rats tend to sign-track. Laser-induced inhibition of VTA dopamine neurons during cue presentation prevented the development of sign-tracking behavior, without affecting goal-tracking behavior. When laser inhibition was terminated, these same rats developed a sign-tracking response. Video analysis using DeepLabCutTM revealed that, relative to rats that received laser inhibition, rats in the control group spent more time near the location of the reward cue even when it was not present and were more likely to orient toward and approach the cue during its presentation. These findings demonstrate that cue-elicited dopamine release is critical for the attribution of incentive salience to reward cues. [ABSTRACT FROM AUTHOR]

Reward-related activity in the dopaminergic midbrain is thought to guide animal behavior, in part by boosting the perceptual and attentional processing of reward-predictive environmental stimuli. In line with this incentive salience hypothesis, studies of human visual search have shown that simple synthetic stimuli, such as lines, shapes, or Gabor patches, capture attention to their location when they are characterized by reward-associated visual features, such as color. In the real world, however, we commonly search for members of a category of visually heterogeneous objects, such as people, cars, or trees, where category examples do not share low-level features. Is attention captured to examples of a reward-associated real-world object category? Here, we have human participants search for targets in photographs of city and landscapes that contain task-irrelevant examples of a reward-associated category. We use the temporal precision of EEG machine learning and ERPs to show that these distractors acquire incentive salience and draw attention, but do not capture it. Instead, we find evidence of rapid, stimulus-triggered attentional suppression, such that the neural encoding of these objects is degraded relative to neutral objects. Humans appear able to suppress the incentive salience of reward-associated objects when they know these objects will be irrelevant, supporting the rapid deployment of attention to other objects that might be more useful. Incentive salience is thought to underlie key behaviors in eating disorders and addiction, among other conditions, and the kind of suppression identified here likely plays a role in mediating the attentional biases that emerge in these circumstances. [ABSTRACT FROM AUTHOR]

Events in life can be perceived to be under our own control, or to occur independently from our will, two psychological styles known as "internal" vs "external locus-of-control" respectively. While it is established that positive events like reward-predicting stimuli attract attention, whether the control over reward gain can also influence the attentional salience of reward cues is unknown. Here, we systematically manipulated the control in reward gain to investigate this possibility in humans. Experiment 1 showed that stimuli associated with an internal control in reward attainment gained attentional salience. However, Experiment 2 showed that the internal control alone is not sufficient to confer attentional salience to reward-cues. Finally, Experiment 3 replicated the results of Experiment 1 and served also the purpose to exclude alternative accounts. Our findings show that the reward-cue attentional salience is not only affected by reward value, but also by the control over reward gain. [ABSTRACT FROM AUTHOR]

Introduction: The abnormal hyperreactivity to food cues in individuals with binge eating behaviors could be regulated by hedonic or reward-based system, overriding the homeostatic system. The aimof the present study was to investigate whether attentional bias for food cues is affected by the level of hunger, maintaining the normal homeostatic system in individuals with binge eating behaviors. Methods: A total of 116 female participants were recruited and divided into four groups: hungry-binge eating group (BE) (n = 29), satiated BE (n = 29), hungry-control (n = 29), satiated control (n = 29). While participants completed a free-viewing task on high or low-calorie food cues, visual attentional processes were recorded using an eye tracker. Results: The results revealed that BE group showed longer initial fixation duration toward high-calorie food cues in both hunger and satiety condition in the early stage, whereas the control group showed longer initial fixation duration toward high-calorie food cues only in hunger conditions. Moreover, in the late stage, the BE group stared more at the high-calorie food cue, compared to control group regardless of hunger and satiety. Discussion: The findings suggest that automatic attentional bias for food cues in individuals with binge eating behaviors occurred without purpose or awareness is not affected by the homeostatic system, while strategic attention is focused on high-calorie food. Therefore, the attentional processing of food cues in binge eating group is regulated by hedonic system rather than homeostatic system, leading to vulnerability to binge eating. [ABSTRACT FROM AUTHOR]

Roughly 20–30% of patients with Attention-deficit/hyperactivity disorder (ADHD) fail to respond to central stimulant (CS) medication. Genetic, neuroimaging, biochemical and behavioral biomarkers for CS response have been investigated, but currently there are no biomarkers available for clinical use that help identify CS responders and non-responders. In the present paper, we studied if incentive salience and hedonic experience evaluated after a single-dose CS medication could predict response and non-response to CS medication. We used a bipolar visual analogue 'wanting' and 'liking' scale to gauge incentive salience and hedonic experience in 25 healthy controls (HC) and 29 ADHD patients. HC received 30 mg methylphenidate (MPH) and ADHD patients received either MPH or lisdexamphetamine (LDX) as selected by their clinician, with dosage individually determined for optimal effect. Clinician-evaluated global impression – severity (CGI-S) and improvement (CGI-I) and patient-evaluated improvement (PGI-I) were used to assess response to CS medication. Resting state functional magnetic resonance imaging (fMRI) was conducted before and after single-dose CS to correlate wanting and liking scores to changes in functional connectivity. Roughly 20% of the ADHD patients were CS non-responders (5 of 29). CS responders had significantly higher incentive salience and hedonic experience scores compared to healthy controls and CS non-responders. Resting state fMRI showed that wanting scores were significantly associated to changes in functional connectivity in ventral striatum including nucleus accumbens. Incentive salience and hedonic experience evaluated after a single-dose CS medication segregate CS responders and non-responders, with corresponding neuroimaging biomarkers in the brain reward system. [ABSTRACT FROM AUTHOR]

Brain-based interventions are needed to address persistent relapse in alcohol use disorder (AUD). Neuroimaging evidence suggests higher frontal connectivity as well as higher within-network connectivity of theoretically defined addiction networks are associated with reduced relapse rates and extended abstinence during follow-up periods. /Hypothesis: A longitudinal randomized double-blind sham-controlled clinical trial investigated whether a non-invasive neuromodulation intervention delivered during early abstinence can (i) modulate connectivity of addiction networks supporting abstinence and (ii) improve relapse rates. Hypotheses: Active transcranial direct current stimulation (tDCS) will (i) increase connectivity of addiction networks known to support abstinence and (ii) reduce relapse rates. Short-term abstinent AUD participants (n = 60) were assigned to 5 days of either active tDCS or sham during cognitive training. Causal discovery analysis (CDA) examined the directional influence from left dorsolateral prefrontal cortex (LDLPFC, stimulation site) to addiction networks that support abstinence. Active tDCS had an effect on the average strength of CDA-determined connectivity from LDLPFC to the incentive salience and negative emotionality addiction networks - increasing in the active tDCS group only. Active tDCS had an effect on relapse rates following the intervention, with lower probability of relapse in the active tDCS vs. sham. Active tDCS showed an unexpected sex-dependent effect on relapse rates. Our results suggest that LDLPFC stimulation delivered during early abstinence has an effect on addiction networks supporting abstinence and on relapse rates. The unexpected sex-dependent neuromodulation effects need to be further examined in larger clinical trials. • Brain-based interventions designed to reduce relapse in AUD are needed. • tDCS + cognitive training intervention delivered during short-term abstinence in AUD. • Intervention increased connectivity from LDLPFC to incentive salience network. • Intervention reduced probability of relapse during follow-up. • Non-invasive stimulation to LDLPFC is a promising intervention for AUD. [ABSTRACT FROM AUTHOR]

Background and aims: The Pavlovian-to-instrumental transfer (PIT) effect is a phenomenon that Pavlovian conditioned cues that could influence one's instrumental behavior. In several substance and behavioral addictions, such as tobacco use disorder and gambling disorder, addiction-related cues could promote independently trained instrumental drug-seeking/drug-taking behaviors, indicating a specific PIT effect. However, it is unclear whether Internet gaming disorder (IGD) would show a similar change in PIT effects as other addictions. The study aimed to explore the specific PIT effects in IGD. Methods: We administrated a PIT task to individuals with IGD (n = 40) and matched health controls (HCs, n = 50), and compared the magnitude of specific PIT effects between the two groups. The severity of the IGD symptoms was assessed by the Chinese version 9-item Internet Gaming Disorder Scale (IGDS) and the Internet Addiction Test (IAT). Results: We found that: (1) related to the HCs group, the IGD group showed enhanced specific PITgame effects, where gaming-related cues lead to an increased choice rate of gaming-related responses; (2) in the IGD group, the magnitude of specific PITgame effects were positively correlated with IAT scores (rho = 0.39, p = 0.014). Discussion and conclusions: Individuals with IGD showed enhanced specific PIT effects related to HCs, which were associated with the severity of addictive symptoms. Our results highlighted the incentive salience of gaming-related cues in IGD. [ABSTRACT FROM AUTHOR]

Most people sample addictive drugs, but use becomes disordered in only a smallminority. Two important factors that influence susceptibility to addiction are individual differences in personality traits and biological sex. The influence of traits on addiction-like behavior is well-characterized in preclinical models of cocaine selfadministration, but less is understood in regards to opioids. How biological sex influences trait susceptibility to opioid self-administration is likewise less studied than psychostimulants. Thus, we sought to elucidate how biological sex and several addiction-relevant traits interact with the propensity to self-administer the opioid remifentanil. We first screened female (n = 19) and male (n = 19) rats for four addiction-relevant traits: impulsivity, novelty place-preference, anxiety-like behavior, and attribution of incentive value to reward cues. Rats were then trained to self-administer remifentanil in a "conflict model" of drug self-administration. Rats had to endure an electric shock to access the response manipulandum that triggered an intravenous infusion of remifentanil. Inmale rats, high anxiety-like behavior was positively correlated with the number of drug infusions if the shock level was low or completely absent. In females, sign-tracking was predictive of greater resistance to punishment during drug seeking; an effect that was mediated by anxiety-like behavior. Females consumed more remifentanil under all conditions, and their drug seeking persisted in the face of significantly greater current than males. These findings demonstrate that the influence of behavioral traits over the propensity to self-administer opioids is dependent upon biological sex. [ABSTRACT FROM AUTHOR]

Rationale : After a history of intermittent cocaine intake, rats develop patterns of drug use characteristic of substance use disorder. The dorsal striatum is involved in the increased pursuit of cocaine after intermittent drug self-administration experience. Within the dorsal striatum, chronic cocaine use changes metabotropic glutamate type II receptor (mGlu2/3) density and function. Objectives: We examined the extent to which activity at Glu2/3 receptors mediates responding for cocaine after intermittent cocaine use. Methods: Male (n = 11) and female (n = 10) Wistar rats self-administered 0.25 mg/kg/infusion cocaine during 10 daily intermittent access (IntA) sessions (5 min ON/25 min OFF, for 5 h/session). We then examined the effects of microinjections of the mGlu2/3 receptor agonist LY379268 (0, 1, and 3 µg/hemisphere) into the ventrolateral part of the dorsal striatum on cocaine self-administration under a progressive ratio schedule of reinforcement. Results: Across 10 IntA sessions, the sexes showed similar levels of cocaine intake. In females only, locomotion significantly increased over sessions, suggesting that female rats developed psychomotor sensitization to self-administered cocaine. After 10 IntA sessions, intra-dorsal striatum LY379268 significantly reduced breakpoints achieved for cocaine, active lever presses, and cocaine infusions earned under progressive ratio. LY379268 had no effects on locomotion or inactive lever presses, indicating no motor effects. Conclusions: These results suggest that mGlu2/3 receptor activation in the ventrolateral dorsal striatum suppresses incentive motivation for cocaine, and this holds promise for new treatments to manage substance use disorder. [ABSTRACT FROM AUTHOR]

While some individuals can defy the lure of temptation, many others find appetizing food irresistible. The goal of this study was to investigate the neuropsychological mechanisms that increase individuals' vulnerability to cue-induced eating. Using ERPs, a direct measure of brain activity, we showed that individuals with larger late positive potentials in response to food-related cues than to erotic images are more susceptible to cue-induced eating and, in the presence of a palatable food option, eat more than twice as much as individuals with the opposite brain reactivity profile. By highlighting the presence of individual brain reactivity profiles associated with susceptibility to cue-induced eating, these findings contribute to the understanding of the neurobiological basis of vulnerability to obesity.

Rationale: Acetylcholinergic antagonists have shown some promise in reducing addiction-related behaviors in both preclinical and clinical studies. However, the psychological mechanisms by which these drugs are able to affect addictive behavior remain unclear. A particular key process for the development of addiction is the attribution of incentive salience to reward-related cues, which can be specifically measured in animals using a Pavlovian conditioned approach procedure. When confronted with a lever that predicts food delivery, some rats engage with the lever directly (i.e., they sign track), indicating attribution of incentive-motivational properties to the lever itself. In contrast, others treat the lever as a predictive cue and approach the location of impending food delivery (i.e., they goal track), without treating the lever itself as a reward. Objectives: We tested whether systemic antagonism of the either nicotinic or muscarinic acetylcholine receptors would selectively affect sign- or goal-tracking behavior, indicating a selective effect on incentive salience attribution. Methods: A total of 98 male Sprague Dawley rats were either given the muscarinic antagonist scopolamine (100, 50, or 10 µg/kg i.p.) or the nicotinic antagonist mecamylamine (0.3, 1.0, or 3 mg/kg i.p.) before being trained on a Pavlovian conditioned approach procedure. Results: Scopolamine dose-dependently decreased sign tracking behavior and increased goal-tracking behavior. Mecamylamine reduced sign-tracking but did not affect goal-tracking behavior. Conclusions: Antagonism of either muscarinic or nicotinic acetylcholine receptors can reduce incentive sign-tracking behavior in male rats. This effect appears to be specifically due to a reduction in incentive salience attribution since goal-tracking either increased or was not affected by these manipulations. [ABSTRACT FROM AUTHOR]

Model-free and model-based computations are argued to distinctly update action values that guide decision-making processes. It is not known, however, if these model-free and model-based reinforcement learning mechanisms recruited in operationally based instrumental tasks parallel those engaged by pavlovian-based behavioral procedures. Recently, computational work has suggested that individual differences in the attribution of incentive salience to reward predictive cues, that is, sign- and goaltracking behaviors, are also governed by variations in model-free and model-based value representations that guide behavior. Moreover, it is not appreciated if these systems that are characterized computationally using model-free and model-based algorithms are conserved across tasks for individual animals. In the current study, we used a within-subject design to assess sign-tracking and goal-tracking behaviors using a pavlovian conditioned approach task and then characterized behavior using an instrumental multistage decision-making (MSDM) task in male rats. We hypothesized that both pavlovian and instrumental learning processes may be driven by common reinforcement-learning mechanisms. Our data confirm that sign-tracking behavior was associated with greater reward-mediated, model-free reinforcement learning and that it was also linked to model-free reinforcement learning in the MSDM task. Computational analyses revealed that pavlovian model-free updating was correlated with model-free reinforcement learning in the MSDM task. These data provide key insights into the computational mechanisms mediating associative learning that could have important implications for normal and abnormal states. [ABSTRACT FROM AUTHOR]

The ability of environmental cues to trigger alcohol-seeking behaviours is thought to facilitate problematic alcohol use. Individuals' tendency to attribute incentive salience to cues may increase the risk of addiction. We sought to study the relationship between incentive salience and alcohol addiction using non-preferring rats to model the heterogeneity of human alcohol consumption, investigating both males and females. Adult rats were subjected to the alcohol deprivation effect (ADE) paradigm, where they were given voluntary access to different alcohol solutions with repeated interruptions by deprivation and reintroduction phases over a protracted period (five Alcohol Deprivation Cycles). Before each Alcohol Deprivation Cycle, rats were tested in the Pavlovian Conditioned Approach (PCA) paradigm, which quantifies the individual salience toward a conditional cue and the reward, thus allowing us to trace the process of attributing incentive salience to reward cues. During the final Alcohol Deprivation Cycle (ADE5), animals were tested for compulsive-like behaviour using quinine taste adulteration. We investigated sex differences in drinking behaviour and PCA performance. We observed thatb females drank significantly more alcohol than males and displayed more sign-tracking (ST) behaviour in the PCA, whereas males showed goal-tracking (GT) behaviour. Furthermore, we found that high drinkers exhibited more ST behaviour. The initial PCA phenotype was correlated with later alcohol consumption. Our findings indicate a complex relationship between incentive salience and alcohol addiction and emphasize the importance of considering both sexes in preclinical research., (© 2025 The Author(s). Addiction Biology published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.)

Previous research suggests the amplitude of the P3 event-related potential (ERP) response reflects the incentive value of the eliciting stimulus, and that individuals with trait-like lower sensitivity (LS) to the acute effects of alcohol, a potent risk factor for alcohol use disorder (AUD), tend to show exaggerated P3 ERP responses to alcohol beverage cues (compared to their peers with higher sensitivity; HS). No prior research has examined trajectories of the cue-elicited P3 response across repeated trials of nonreinforced cue presentations. Characterizing these trajectories can be informative as to potential mechanisms linking LS with increased AUD risk. Here, we tested whether individual differences in alcohol sensitivity are associated with different trial-by-trial trajectories of the P3 elicited by alcohol and nonalcohol reward cues (infrequent oddball/target stimuli) using a large sample of emerging adults (Mage= 19.53; N = 287; 55% female; 86% White; 90% right-handed) stratified for alcohol sensitivity. Multilevel models adjusted for age, sex, handedness, and alcohol use indicated that: (i) the P3 response to alcohol and nonalcohol reward cues alike sensitized (i.e., increased) across trials; (ii) across the task, the P3 response to alcohol cues was larger for the LS than the HS phenotype; and (iii) the P3 difference score (alcohol - nonalcohol) was larger for the LS than HS phenotype only across the first half of task. Findings suggest that whereas incentive value attribution may be a mechanism for alcohol cue-triggered attentional biases for both LS and HS individuals, LS individuals more consistently over-attribute incentive value to alcohol cues.

Research shows cognitive and neurobiological overlap between sign‐tracking [value‐modulated attentional capture (VMAC) by response‐irrelevant, discrete cues] and maladaptive behaviour (e.g. substance abuse). We investigated the neural correlates of sign‐tracking in 20 adults using an additional singleton task (AST) and functional magnetic resonance imaging (fMRI). Participants responded to a target to win monetary reward, the amount of which was signalled by singleton type (reward cue: high value vs. low value). Singleton responses resulted in monetary deductions. Sign‐tracking—greater distraction by high‐value vs. low‐value singletons (H > L)—was observed, with high‐value singletons producing slower responses to the target than low‐value singletons. Controlling for age and sex, analyses revealed no differential brain activity across H > L singletons. Including sign‐tracking as a regressor of interest revealed increased activity (H > L singletons) in cortico‐subcortical loops, regions associated with Pavlovian conditioning, reward processing, attention shifts and relative value coding. Further analyses investigated responses to reward feedback (H > L). Controlling for age and sex, increased activity (H > L reward feedback) was found in regions associated with reward anticipation, attentional control, success monitoring and emotion regulation. Including sign‐tracking as a regressor of interest revealed increased activity in the temporal pole, a region related to value discrimination. Results suggest sign‐tracking is associated with activation of the 'attention and salience network' in response to reward cues but not reward feedback, suggesting parcellation between the two at the level of the brain. Results add to the literature showing considerable overlap in neural systems implicated in reward processing, learning, habit formation, emotion regulation and substance craving. [ABSTRACT FROM AUTHOR]

The attribution of incentive salience to reward-paired cues is dependent on dopamine release in the nucleus accumbens core (NAcC). These dopamine signals conform to traditional reward-prediction error signals and have been shown to diminish with time. Here we examined whether the diminishing dopamine signal in the NAcC has functional implications for the expression of sign-tracking, a Pavlovian conditioned response indicative of the attribution of incentive salience to reward-paired cues. Food-restricted male Sprague Dawley rats were trained in a Pavlovian paradigm in which an insertable lever predicted delivery of food reward in a nearby food cup. After 7 or 14 training sessions, rats received infusions of saline, the dopamine antagonist flupenthixol, or the GABA agonists baclofen and muscimol into the NAcC or the dorsal lateral striatum (DLS). Dopamine antagonism within the NAcC attenuated sign-tracking, whereas reversible inactivation did not affect sign-tracking but increased non-specific food cup checking behaviors. Neither drug in the DLS affected sign-tracking behavior. Critically, extended training did not alter these effects. Although extended experience with an incentive stimulus may reduce cue-evoked dopamine in the NAcC, this does not remove the dependence on dopamine in this region to promote Pavlovian cue approach nor result in the recruitment of dorsal lateral striatal systems for this behavior. These data support the notion that dopamine within the mesoaccumbal system, but not the nigrostriatal system, contributes critically to incentive motivational processes independent of the length of training.

Behavioural economists have identified many psychological manipulations which affect perceived value. A prominent example of this is bundling, in which several small gains (or costs) are experienced as more valuable (or costly) than if the same total amount is presented together. While extensively demonstrated in humans, to our knowledge this effect has never been investigated in an animal, let alone an invertebrate. We trained individual Lasius niger workers to two of three conditions in which either costs (travel distance), gains (sucrose reward), or both were either bundled or segregated: (1) both costs and gains bundled, (2) both segregated, and (3) only gains segregated. We recorded pheromone deposition on the ants’ return trips to the nest as measure of perceived value. After training, we offer the ants a binary choice between odours associated with the treatments. While bundling treatment did not affect binary choice, it strongly influenced pheromone deposition. Ants deposited c. 80% more pheromone when rewards were segregated but costs bundled as compared with both costs and rewards being bundled. This pattern is further complicated by the pairwise experience each animal made, and which of the treatments it experiences first during training. This demonstrates that even insects are influenced by bundling effects. We propose that the deviation between binary choice and pheromone deposition in this case may be due to a possible linearity in distance perception in ants, while almost all other sensory perception in animals is logarithmic.

In the "suboptimal choice" procedure, pigeons, but not rats, systematically choose an alternative associated with stimuli that indicate the presence or absence of a reward and with a smaller probability of reinforcement, over another option associated with noninformative stimuli, and a higher probability of reinforcement. To explain these opposite preferences, it has been proposed that rats and pigeons have a differential sensitivity to the conditioned inhibition that emerges from the stimulus that predicts non-reinforcement: While it does not have an impact in pigeons, it strongly influences rats' preferences. Alternatively, it was recently proposed that there is not a fundamental difference in the behavior of rats and pigeons, but that the procedure employed to evaluate each of these species has generated the difference; in particular, it was proposed that both species prefer the discriminative alternative when the discriminative stimuli have incentive salience. In this paper we review the theoretical assumptions underlying these proposals because the evidence regarding the incentive salience of the stimuli has found contradictory results. Finally, future theoretical suggestions are made to resolve these differences in results in the theoretical proposals to explain the differences between species in the "suboptimal choice" procedure. [ABSTRACT FROM AUTHOR]

The paraventricular nucleus of the thalamus (PVT) has been implicated in behavioral responses to reward-associated cues. However, the precise role of the PVT in these behaviors has been difficult to ascertain since Pavlovian-conditioned cues can act as both predictive and incentive stimuli. The "sign-tracker/goal-tracker" rat model has allowed us to further elucidate the role of the PVT in cue-motivated behaviors, identifying this structure as a critical component of the neural circuitry underlying individual variation in the propensity to attribute incentive salience to reward cues. The current study assessed differences in the engagement of specific PVT afferents and efferents in response to presentation of a food-cue that had been attributed with only predictive value or with both predictive and incentive value. The retrograde tracer fluorogold (FG) was injected into the PVT or the nucleus accumbens (NAc) of rats, and cue-induced c-Fos in FG-labeled cells was quantified. Presentation of a predictive stimulus that had been attributed with incentive value elicited c-Fos in PVT afferents from the lateral hypothalamus, medial amygdala (MeA), and the prelimbic cortex (PrL), as well as posterior PVT efferents to the NAc. PVT afferents from the PrL also showed elevated c-Fos levels following presentation of a predictive stimulus alone. Thus, presentation of an incentive stimulus results in engagement of subcortical brain regions; supporting a role for the hypothalamic-thalamic-striatal axis, as well as the MeA, in mediating responses to incentive stimuli; whereas activity in the PrL to PVT pathway appears to play a role in processing the predictive qualities of reward-paired stimuli.

RationaleDisorders of behavioral regulation, including attention deficit hyperactivity disorder (ADHD) and drug addiction, are in part due to poor inhibitory control, attentional deficits, and hyper-responsivity to reward-associated cues.ObjectivesTo determine whether these traits are related, we tested genetically variable male and female heterogeneous stock rats in the choice reaction time (CRT) task and Pavlovian conditioned approach (PavCA). Sex differences in the response to methylphenidate during the CRT were also assessed.MethodsIn the CRT task, rats were required to withhold responding until one of two lights indicated whether responses into a left or right port would be reinforced with water. Reaction time on correct trials and premature responses were the operational definitions of attention and response inhibition, respectively. Rats were also pretreated with oral methylphenidate (0, 2, 4 mg/kg) during the CRT task to determine whether this drug would improve performance. Subsequently, during PavCA, presentation of an illuminated lever predicted the delivery of a food pellet into a food-cup. Lever-directed approach (sign-tracking) and food-cup approach (goal-tracking) were the primary measures, and rats were categorized as "sign-trackers" and "goal-trackers" using an index based on these measures.ResultsSign-trackers made more premature responses than goal-trackers but showed no differences in reaction time. There were sex differences in both tasks, with females having higher sign-tracking, completing more CRT trials, and making more premature responses after methylphenidate administration.ConclusionsThese results indicate that response inhibition is related to reward-cue responsivity, suggesting that these traits are influenced by common genetic factors.

Aims: This study used a behavioral approach‐avoidance task including images of alcoholic beverages to test whether low sensitivity to alcohol (LS) is a phenotypical marker of a dispositional propensity to attribute bottom‐up incentive value to naturally conditioned alcohol cues. Design, setting and participants: Experimental study with a measured individual difference variable at a university psychology laboratory in Missouri, MO, USA. Participants were 178 emerging adults (aged 18–20 years) varying in self‐reported sensitivity to alcohol's acute effects. Measurements Participants completed the alcohol approach‐avoidance task while behavior (response time; RT) and the electroencephalogram (EEG) were recorded. Stimulus‐locked event‐related potentials (ERPs) provided indices of integrated (top‐down and bottom‐up) stimulus incentive value (P3 amplitude) and conflict between top‐down task demands and bottom‐up response propensities (N450 amplitude). Findings Linear mixed models showed faster RT for 'alcohol‐approach' relative to 'alcohol‐avoid' trials for lower‐sensitivity (LS) [meanD ± standard errorD (MD ± SED) = 29.51 ± 9.74 ms, t(328) = 3.03, P = 0.003] but not higher‐sensitivity (HS) individuals (MD ± SED = 2.27 ± 9.33 ms, t(328) = 0.243, P = 0.808). There was enhanced N450 amplitude (response conflict) for alcohol‐avoid relative to alcohol‐approach trials for LS participants (MD ± SED = 0.811 ± 0.198 μV, Z = 4.108, P < 0.001) and enhanced N450 amplitude for alcohol‐approach relative to alcohol‐avoid for HS participants (MD ± SED = 0.419 ± 0.188 μV, Z = 2.235, P = 0.025). There was also enhanced P3 amplitude for alcohol‐approach relative to alcohol‐avoid for LS (MD ± SED = 0.825 ± 0.204 μV, Z = 4.045, P < 0.001) but not HS (MD ± SED = 0.013 ± 0.194 μV, Z = 0.068, P = 0.946). Conclusions: Findings from a human laboratory study appear to support the notion that low sensitivity to alcohol indexes a propensity to attribute bottom–up incentive value to naturally conditioned alcohol cues. [ABSTRACT FROM AUTHOR]

We present a multi-attribute incentive salience (MAIS) model as a computational account of incentive salience in model-based Pavlovian learning. A model of incentive salience as a joint function of reward value and physiological state has been previously proposed by Zhang et al. (2009). In that model, the function takes additive or multiplicative forms depending on whether a preference shifts from positive to negative or vice versa. We demonstrate that arbitrarily varying this function is unnecessary to explain observed data. A multiplicative function is sufficient if one takes into account empirical data suggesting the incentive salience function for an incentive is comprised of multiple physiological signals. We compare our model to the previously proposed model on two datasets. We find the MAIS model predicts the outcomes equally well, fits empirical data describing multiple sensory representations of a single stimulus, better approximates the dual-structure appetitive-aversive nature of the reward system, is compatible with existing knowledge about incentive salience in Pavlovian learning, and better describes revaluation in Pavlovian learning. This model addresses a call (Dayan & Berridge, 2014) for algorithmic and computational models of model-based Pavlovian learning that consistently and fully explain empirical observations. Because a multi-attribute model is relevant even for simple Pavlovian associations, it should be useful in a wide variety of decision-making contexts, including agent modeling and addiction research. [ABSTRACT FROM AUTHOR]

Rationale: Relapse often occurs when individuals are exposed to stimuli or cues previously associated with the drug-taking experience. The ability of drug cues to trigger relapse is believed to be a consequence of incentive salience attribution, a process by which the incentive value of reward is transferred to the reward-paired cue. Sign-tracker (ST) rats that attribute enhanced incentive value to reward cues are more prone to relapse compared to goal-tracker (GT) rats that primarily attribute predictive value to such cues. Objectives: The neurobiological mechanisms underlying this individual variation in relapse propensity remains largely unexplored. The paraventricular nucleus of the thalamus (PVT) has been identified as a critical node in the regulation of cue-elicited behaviors in STs and GTs, including cue-induced reinstatement of drug-seeking behavior. Here we used a chemogenetic approach to assess whether "top-down" cortical input from the prelimbic cortex (PrL) to the PVT plays a role in mediating individual differences in relapse propensity. Results: Chemogenetic inhibition of the PrL-PVT pathway selectively decreased cue-induced reinstatement of drug-seeking behavior in STs, without affecting behavior in GTs. In contrast, cocaine-primed drug-seeking behavior was not affected in either phenotype. Furthermore, when rats were characterized based on a different behavioral phenotype—locomotor response to novelty—inhibition of the PrL-PVT pathway had no effect on either cue- or drug-induced reinstatement. Conclusions: These results highlight an important role for the PrL-PVT pathway in vulnerability to relapse that is consequent to individual differences in the propensity to attribute incentive salience to discrete reward cues. [ABSTRACT FROM AUTHOR]

Internet use for nearly all daily activities has escalated over the last twenty years as an adaptive response to increased provision of devices, programs, and access. Positive results include increased connectivity and negative results include maladaptive internet use (MIU), frequently investigated in youth under a variety of names, despite the lack of concordance on a model. Common factors identified include age, male gender, amotivation for responsibilities, depressive symptomology, and low self-efficacy. There is a distinct absence of research on adult populations, hindering full development of the concept of MIU. The focus of this research was to assess the relationship between levels of internet use and depression, self-efficacy, age, and gender in an adult population in Hong Kong. A quantitative correlational online survey design was employed to assess the levels of the above in a sample of residents. Participants (n = 203) included in the survey were English speaking adults, aged between 22 and 65, resident in Hong Kong, representing twenty-eight nationalities, with 32.51 percent male (n = 66), and 67.48 percent female (n = 137). The survey consisted of inventories for Internet Addiction, Depression, Self-Efficacy, and demographic items. MIU was significantly correlated with depression, age, and self-efficacy, but not gender. There is an adult population who present with significantly maladaptive internet use patterns correlated with depression, low self-efficacy, and lower age, which could significantly impact youth MIU, where adults provide guidance and modelling of behaviors. The absence of a standardized definition greatly hinders the provision of adequate awareness, diagnosis, treatment, and prevention measures for all. [ABSTRACT FROM AUTHOR]

• Neural and psychological indicators of salience processing are examined in creatives. • Creativity is associated with diminished ERP responses to oddball stimuli. • Creativity predicts greater overall wanting of, and positive thoughts about, rewards. • Atypical salience processing may play an under-explored role in creative thinking. Creativity has previously been linked with various attentional phenomena, including unfocused or broad attention. Although this has typically been interpreted through an executive functioning framework, such phenomena may also arise from atypical incentive salience processing. Across two studies, we examine this hypothesis both neurally and psychologically. First we examine the relationship between figural creativity and event-related potentials during an audio-visual oddball task, finding that rater creativity of drawings is associated with a diminished P300 response at midline electrodes, while abstractness and elaborateness of the drawings is associated with an altered distribution of the P300 over posterior electrodes. These findings support the notion that creativity may involve an atypical attribution of salience to prominent information. We further explore the incentive salience hypothesis by examining relationships between creativity and a psychological indicator of incentive salience captured by participants' ratings of enjoyment (liking) and their motivation to pursue (wanting) diverse real world rewards, as well as their positive spontaneous thoughts about those rewards. Here we find enhanced motivation to pursue activities as well as a reduced relationship between the overall tendency to enjoy rewards and the tendency to pursue them. Collectively, these findings indicate that creativity may be associated with atypical allocation of attentional and motivational resources to novel and rewarding information, potentially allowing more types of information access to attentional resources and motivating more diverse behaviors. We discuss the possibility that salience attribution in creatives may be less dependent on task-relevance or hedonic pleasure, and suggest that atypical salience attribution may represent a trait-like feature of creativity. [ABSTRACT FROM AUTHOR]

Background and aims: In susceptible individuals, cues associated with drug use are theorized to take on incentive–motivational properties, including the ability to reinforce higher‐order, drug‐related associative learning. This study aimed to test this prediction among people varying in risk for alcohol use disorder. Design, setting and participants: Repeated‐measures experiment with a measured individual difference variable at a University psychology laboratory in Missouri, USA. One hundred and six young adults (96 contributed complete data) were pre‐selected to represent the upper and lower quartiles of self‐reported sensitivity to alcohol's acute effects. Measurements Participants completed a second‐order Pavlovian conditioning paradigm in which an initially neutral visual cue (second‐order conditional stimulus; CS2) predicted onset of an olfactory cue (first‐order conditional stimulus; CS1). Olfactory cues were isolated from alcoholic beverages, sweets and non‐comestible substances, each presumed to have a natural history of first‐order conditioning. Event‐related potential responses to the CS2 across its conditioning and extinction, and to the CS1, provided neurophysiological indices of incentive salience (IS). Findings The IS of the alcohol CS1 was higher among participants low in alcohol sensitivity (LS), relative to their higher‐sensitivity (HS) peers. The IS of the CS2 paired with the alcohol CS1 increased across the CS2 conditioning phase among LS but not HS participants. Also, LS (but not HS) individuals also experienced increases in alcohol craving following alcohol CS1 exposure, and this change was correlated with increases in the IS of the CS2 paired with the alcohol CS1. Conclusions: Alcoholic beverage odor, a proximal cue for alcohol consumption, appears to reinforce conditioning of neurophysiological responses to a novel cue among low alcohol sensitivity (LS) individuals but not high alcohol sensitivity individuals, providing the first evidence that the LS phenotype may be associated with differences in the conditioned reinforcing properties of alcohol‐related cues. These findings support the idea that the LS phenotype may increase alcohol use disorder risk via susceptibility to incentive salience sensitization. [ABSTRACT FROM AUTHOR]

In this review, we highlight evidence that supports a role for the paraventricular nucleus of the thalamus (PVT) in motivated behavior. We include a neuroanatomical and neurochemical overview, outlining what is known of the cellular makeup of the region and its most prominent afferent and efferent connections. We discuss how these connections and distinctions across the anterior-posterior axis correspond to the perceived function of the PVT. We then focus on the hypothalamic-thalamic-striatal circuit and the neuroanatomical and functional placement of the PVT within this circuit. In this regard, the PVT is ideally positioned to integrate information regarding internal states and the external environment and translate it into motivated actions. Based on data that has emerged in recent years, including that from our laboratory, we posit that orexinergic (OX) innervation from the lateral hypothalamus (LH) to the PVT encodes the incentive motivational value of reward cues and thereby alters the signaling of the glutamatergic neurons projecting from the PVT to the shell of the nucleus accumbens (NAcSh). The PVT-NAcSh pathway then modulates dopamine activity and resultant cue-motivated behaviors. As we and others apply novel tools and approaches to studying the PVT we will continue to refine the anatomical, cellular, and functional definitions currently ascribed to this nucleus and further elucidate its role in motivated behaviors. [ABSTRACT FROM AUTHOR]