Drug-related Stimuli Research Articles

Anterior insula activation during inhibition to smoking cues is associated with ability to maintain tobacco abstinence

Relapse to smoking after initial abstinence is a major clinical challenge with significant public health consequences. At the brain and behavioral level, those who relapse to tobacco smoking have both greater cue-reactivity and lower inhibitory control than those who remain abstinent. Little is known about neural activation during inhibitory control tasks in the presence of drug-related cues. In the current study, tobacco smokers (SMK; n = 22) and non-smoking controls (CON; n = 19) completed a Go/NoGo task involving smoking cues during a functional magnetic resonance imaging (fMRI) scan. Following the scan session, smokers were required to quit smoking, and maintenance of abstinence was evaluated as part of a 12-week smoking cessation trial. We evaluated pre-cessation brain activity during NoGo trials in smokers who were versus were not able to quit smoking. We then compared fMRI and inhibitory control measures between smokers and non-smokers. We did not find differences between SMK and CON in performance or activation to smoking or neutral cues. However, compared to SMK who relapsed, SMK who attained biochemically-validated abstinence at the end of the smoking cessation trial had greater neural activation in the anterior insula during NoGo trials specifically with smoking-related cues. Results indicate that within SMK, decreased inhibitory control activation during direct exposure to drug-related stimuli may be a marker of difficulty quitting and relapse vulnerability.

Drug Stroop: Mechanisms of response to computerized cognitive behavioral therapy for cocaine dependence in a randomized clinical trial

BackgroundPoor performance on Drug Stroop tasks, which could indicate attentional bias to drug-related cues, craving, poor cognitive control (including poor response inhibition), has been associated with substance use severity, treatment retention and substance use treatment outcomes. Cognitive Behavioral Therapy (CBT) focuses on training in appraisal and coping strategies, including strategies to minimize the negative impact of triggers and coping with drug-cue-induced craving. One mechanism of action of CBT may be the strengthening of cognitive control processes and reduction of attentional bias to drug-related stimuli. MethodsMethadone-maintained individuals with cocaine-use disorders, participating in a randomized controlled trial of treatment as usual (TAU) versus TAU plus access to computer-based CBT (CBT4CBT), completed a computerized Drug Stroop task at pre- and post-treatment. Analyses determined whether attentional bias toward drug-related stimuli changed differentially by treatment group or cocaine use outcomes across the treatment period and whether engagement in components of CBT4CBT or TAU treatment related to changes in attentional bias toward drug-related stimuli at post- versus pre-treatment. ResultsParticipants achieving a longer duration of cocaine abstinence during treatment (3+ weeks) showed greater reductions in Drug Stroop Effect than those with shorter maximum continuous abstinence. Reductions in Drug Stroop Effect across treatment were associated with greater engagement with CBT4CBT-specific treatment components, but not TAU-specific treatment components. ConclusionsReduction in attentional bias to drug-related cues and craving and/or improved executive cognitive control and response inhibition may contribute to the mechanism of action of CBT4CBT.

Left frontoparietal network activity is modulated by drug stimuli in cocaine addiction.

Cocaine addicts present reduced activity in the left frontoparietal network, a brain network associated with cognitive control, during the processing of non-drug reward related stimuli (Costumero et al., Addiction Biology 22:479-489, 2015). However, the involvement of this network in drug-related stimuli processing remains unclear. Here, fifteen cocaine-dependent men and fifteen healthy matched controls viewed cocaine-related, erotic, aversive, and neutral pictures during an fMRI session. Group independent component analysis was then performed to investigate how functional networks were modulated by the different emotional images. The results showed that the cocaine-dependent group showed stronger left frontoparietal network activity during the processing of cocaine-related pictures than the control group. Furthermore, the activity of this network during cocaine image processing was positively associated with the years of cocaine use in addicted subjects. In conclusion, our results indicate that the left frontoparietal network is affected in cocaine-dependent men, and may be related to the cognitive control deficits shown in addiction.

Reduction in N2 amplitude in response to deviant drug-related stimuli during a two-choice oddball task in long-term heroin abstainers.

Chronic heroin use can cause deficits in response inhibition, leading to a loss of control over drug use, particularly in the context of drug-related cues. Unfortunately, heightened incentive salience and motivational bias in response to drug-related cues may exist following abstinence from heroin use. The present study aimed to examine the effect of drug-related cues on response inhibition in long-term heroin abstainers. Sixteen long-term (8-24months) male heroin abstainers and 16 male healthy controls completed a modified two-choice oddball paradigm, in which a neutral "chair" picture served as frequent standard stimuli; the neutral and drug-related pictures served as infrequent deviant stimuli of different conditions respectively. Event-related potentials were compared across groups and conditions. Our results showed that heroin abstainers exhibited smaller N2d amplitude (deviant minus standard) in the drug cue condition compared to the neutral condition, due to smaller drug-cue deviant-N2 amplitude compared to neutral deviant-N2. Moreover, heroin abstainers had smaller N2d amplitude compared with the healthy controls in the drug cue condition, due to the heroin abstainers having reduced deviant-N2 amplitude compared to standard-N2 in the drug cue condition, which reversed in the healthy controls. Our findings suggested that heroin addicts still show response inhibition deficits specifically for drug-related cues after longer-term abstinence. The inhibition-related N2 modulation for drug-related could be used as a novel electrophysiological index with clinical implications for assessing the risk of relapse and treatment outcome for heroin users.

Cannabidiol regulation of emotion and emotional memory processing: relevance for treating anxiety-related and substance abuse disorders.

Learning to associate cues or contexts with potential threats or rewards is adaptive and enhances survival. Both aversive and appetitive memories are therefore powerful drivers of behaviour, but the inappropriate expression of conditioned responding to fear- and drug-related stimuli can develop into anxiety-related and substance abuse disorders respectively. These disorders are associated with abnormally persistent emotional memories and inadequate treatment, often leading to symptom relapse. Studies show that cannabidiol, the main non-psychotomimetic phytocannabinoid found in Cannabis sativa, reduces anxiety via 5-HT1A and (indirect) cannabinoid receptor activation in paradigms assessing innate responses to threat. There is also accumulating evidence from animal studies investigating the effects of cannabidiol on fear memory processing indicating that it reduces learned fear in paradigms that are translationally relevant to phobias and post-traumatic stress disorder. Cannabidiol does so by reducing fear expression acutely and by disrupting fear memory reconsolidation and enhancing fear extinction, both of which can result in a lasting reduction of learned fear. Recent studies have also begun to elucidate the effects of cannabidiol on drug memory expression using paradigms with translational relevance to addiction. The findings suggest that cannabidiol reduces the expression of drug memories acutely and by disrupting their reconsolidation. Here, we review the literature demonstrating the anxiolytic effects of cannabidiol before focusing on studies investigating its effects on various fear and drug memory processes. Understanding how cannabidiol regulates emotion and emotional memory processing may eventually lead to its use as a treatment for anxiety-related and substance abuse disorders. Linked Articles This article is part of a themed section on Pharmacology of Cognition: a Panacea for Neuropsychiatric Disease? To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v174.19/issuetoc.

Do specific NMDA receptor subunits act as gateways for addictive behaviors?

Addiction to alcohol and drugs is a major social and economic problem, and there is considerable interest in understanding the molecular mechanisms that promote addictive drives. A number of proteins have been identified that contribute to expression of addictive behaviors. NMDA receptors (NMDARs), a subclass of ionotropic glutamate receptors, have been of particular interest because their physiological properties make them an attractive candidate for gating induction of synaptic plasticity, a molecular change thought to mediate learning and memory. NMDARs are generally inactive at the hyperpolarized resting potentials of many neurons. However, given sufficient depolarization, NMDARs are activated and exhibit long-lasting currents with significant calcium permeability. Also, in addition to stimulating neurons by direct depolarization, NMDARs and their calcium signaling can allow strong and/or synchronized inputs to produce long-term changes in other molecules (such as AMPA-type glutamate receptors) which can last from days to years, binding internal and external stimuli in a long-term memory trace. Such memories could allow salient drug-related stimuli to exert strong control over future behaviors and thus promote addictive drives. Finally, NMDARs may themselves undergo plasticity, which can alter subsequent neuronal stimulation and/or the ability to induce plasticity. This review will address recent and past findings suggesting that NMDAR activity promotes drug- and alcohol-related behaviors, with a particular focus on GluN2B subunits as possible central regulators of many addictive behaviors, as well as newer studies examining the importance of non-canonical NMDAR subunits and endogenous NMDAR cofactors.

Cognitive dysfunction and underlying neural basis in substance addiction

As one of the most serious public health problems that extract a high toll on individuals and the society as a whole, substance abuse/addiction has attracted much attention from both researchers and the public. According to the DSM-5, substance addiction is a chronically relapsing psychiatric disorder that has been characterized by compulsion to seek and use drugs, loss of control in limiting intake despite serious negative consequences. However, more than 80% of the individuals with addiction fail to seek treatment, perhaps reflecting their cognitive function impairments. Previous studies have showed that most drugs of abuse exert their reinforcing effects and produce euphoria by inducing dopamine surges in limbic regions, which then have cascading effects on other neurotransmitter systems, leading to characteristic plastic adaptions; significant changes in neural circuits implicated in reward, attention, inhibitory control, decision making and interoception; and cognitive dysfunctions. However, much is still to be learned about the neural mechanisms involved in drugs’ effects on cognitive functions and the vicious cycle of “drug abuse – withdrawal – recovery – relapse”. For a better understanding of the causes of substance addiction and its underlying neural mechanisms, we provide an integrative review of behavioral and neuroimaging studies in substance addiction, introduce a neurobiological model of substance addiction, and finally propose future directions for research and clinical treatment. First, we summarize the research on the cognitive and neural mechanisms involved in substance addiction. (1) Drug-related cues can enhance the activities in the mesocorticolimbic system implicated in reward and drug motivation, which then result in increased attention to the drug-related stimuli. Thus, the neural changes in the frontolimbic system may be a potential neural basis for attentional bias toward drugs in individuals with addiction. (2) The deficit in inhibitory control typically observed in individuals with substance addiction may be due to a dysfunction in their prefrontal cortex-striatothalamic circuitry. (3) These individuals’ poor decision making may be a product of an imbalance between three separate, but interacting, neural systems: the amygdala-striatum (an impulsive system); the prefrontal cortex (a reflective system); and the insula (the interoceptive system). (4) Emerging evidence shows that individuals with drug addiction have interoceptive processing deficits, perhaps due to dysfunctions in brain systems such as the insula and the anterior cingulate cortex. Second, we introduce a neurobiological model of substance addiction that depicts addiction as a result of an imbalance of six interactive circuits (i.e., reward, motivation/drive, memory, executive control, mood, and interoception). These brain circuits interact with one another to attain proper inhibitory control and hence good decision making. During addiction, however, the enhanced activities of six circuits (i.e., reward, motivation, memory, executive control, mood, and interoception) overwhelm the PFC’s inhibitory control and hence lead to craving. Finally, we propose that future studies should (1) use multi-modal imaging techniques, (2) pay attention to comorbidity and clarify the association between addiction and other psychiatric disorders, (3) discover more biomarkers and optimize the diagnostic system using both behavioral and neuroimaging information, and (4) develop brain-based intervention techniques. Such studies should deepen our understanding of substance addiction and provide insights to its treatment.

Stimuli associated with the presence or absence of amphetamine regulate cytoskeletal signaling and behavior

Drug-paired stimuli rapidly enlarge dendritic spines in the nucleus accumbens (NAcc). While increases in spine size and shape are supported by rearrangement of the actin cytoskeleton and facilitate the synaptic expression of AMPA-type glutamate receptors, it remains unclear whether drug-related stimuli can influence signaling pathways known to regulate these changes in spine morphology. These pathways were studied in rats trained on a discrimination learning paradigm using subcellular fractionation and protein immunoblotting to isolate proteins within dendritic spine compartments in the NAcc shell. An open field chamber was repeatedly associated with amphetamine in one group (Paired) and explicitly unpaired with amphetamine in another (Unpaired). Rats in a third group were exposed to the open field but never administered amphetamine (Control). When administered saline and returned to the open field one week later, Paired rats as expected displayed a conditioned locomotor response relative to rats in the other two groups. NAcc shell tissues were harvested immediately after this 30-minute test. Re-exposing Paired rats to the drug-paired excitatory context significantly decreased p-GluA2(S880), an effect consistent with reduced internalization of this subunit and increased spine proliferation in these rats. In contrast, re-exposing Unpaired rats to the drug-unpaired context, capable of inhibiting conditioned responding in these animals, significantly decreased levels of both actin binding protein Arp2/3 and p-cofilin, consistent with spine volatility, shrinkage, and inhibition of spine proliferation in these rats. These findings show that contextual stimuli previously associated with either the presence or absence of amphetamine differentially regulate cytoskeletal signaling pathways in the NAcc.

Effects of attention control training on drug abusers' attentional bias and treatment outcome.

Attentional bias for drug-related stimuli (Drug-AB) has been shown to play an important role in drug abuse, drug treatment, and relapse. This study sought to retrain Drug-AB using the Drug Attention Control Training Program (Drug-ACTP) on a sample of Iranian drug abusers. The experimental group (n = 24) received 3 sessions of training with the Drug-ACTP in addition to treatment as usual; the control group (n = 24) received only treatment as usual. All participants completed a demographic questionnaire, the drug-Stroop test, measures of physiological cue reactivity, the Personal Concerns Inventory (a measure of motivational structure), Persian Temptation Scale, Perceived Stress Scale (PSS), Positive Affect and Negative Affect Schedule (PANAS), Situational Confidence Questionnaire (SCQ), and Readiness to Change Questionnaire (RTCQ). All participants were tested at baseline, posttraining, and a 2-month follow-up. A brief, 6-month telephone follow-up was also conducted to monitor their temptation, SCQ, RTCQ, PANAS, and PSS scores; doses of medicine taken; and number of lapses. The results showed that, compared to the control group, the experimental group showed (a) reductions in Drug-AB, temptations to use, doses of medicine, and number of lapses; and (b) increases on the RTCQ and 2 subscales of the SCQ. Regardless of group membership, adaptive motivation was positively correlated with success in achieving therapeutic goals, and negatively associated with doses of methadone taken and number of relapses. It seems that attentional training can be an important addition to methadone maintenance therapy. (PsycINFO Database Record

Effect of Alcohol on Encoding and Consolidation of Memory for Alcohol-Related Images.

Drug and alcohol abusers develop strong memories for drug-related stimuli. Preclinical studies suggest that such memories are a result of drug actions on reward pathways, which facilitate learning about drug-related stimuli. However, few controlled studies have investigated how drugs affect memory for drug-related stimuli in humans. The current study examined the direct effect of alcohol on memory for images of alcohol-related or neutral beverages. Participants received alcohol (0.8g/kg) either before viewing visual images (encoding condition; n=20) or immediately after viewing them (consolidation condition; n=20). A third group received placebo both before and after viewing the images (control condition; n=19). Memory retrieval was tested exactly 48hours later, in a drug-free state. Alcohol impaired memory in the encoding condition and enhanced memory in the consolidation condition, but these effects did not differ for alcohol-related and neutral beverage stimuli. However, in the encoding condition, participants who experienced greater alcohol-induced stimulation exhibited better memory for alcohol-related, but not neutral beverage stimuli. These findings suggest that individual differences in sensitivity to the positive, rewarding effects of alcohol are associated with greater propensity to remember alcohol-related stimuli encountered while intoxicated. As such, stimulant responders may form stronger memory associations with alcohol-related stimuli, which might then influence their drinking behavior.

Brain Activity toward Gaming-Related Cues in Internet Gaming Disorder during an Addiction Stroop Task.

Background and Aims: Attentional bias for drug-related stimuli is a key characteristic for drug addiction. Characterizing the relationship between attentional bias and brain reactivity to Internet gaming-related stimuli may help in identifying the neural substrates that critical to Internet gaming disorder (IGD).Methods: 19 IGD and 21 healthy control (HC) subjects were scanned with functional magnetic resonance imaging while they were performing an addiction Stroop task.Results: Compared with HC group, IGD subjects showed higher activations when facing Internet gaming-related stimuli in regions including the inferior parietal lobule, the middle occipital gyrus and the dorsolateral prefrontal cortex. These brain areas were thought to be involved in selective attention, visual processing, working memory and cognitive control.Discussion and Conclusions: The results demonstrated that compared with HC group, IGD subjects show impairment in both visual and cognitive control ability while dealing with gaming-related words. This finding might be helpful in understanding the underlying neural basis of IGD.

Early social isolation increases persistence of alcohol-seeking behavior in alcohol-related contexts.

Social conditions during rearing are well known to affect adult alcohol consumption, but few experiments have explored the effects of social conditions on behaviors that are related to alcohol dependence, such as the persistence of alcohol seeking. This study compared the effects of isolation (ISO) and interaction (INT) rearing on the persistence of alcohol-seeking behavior. Rats were trained to lever press for a solution of 10% alcohol diluted in water. They were then exposed to a two-component multiple schedule of reinforcement (baseline). Responses in one component were reinforced by a higher rate of alcohol delivery (rich component, variable interval 15 s) and responses in the other component were reinforced by a lower rate of delivery (lean component, variable interval 45 s). The persistence of lever pressing in the presence of each stimulus was then assessed during extinction. The results from baseline showed that response rates in rats in both groups were higher in the rich component than in the lean component, but ISO rats responded significantly more than INT rats in both components. The persistence of responding during extinction in ISO rats in both components was also higher than that in INT rats. The results show that effects of ISO are not restricted to alcohol consumption, but also affect persistence of alcohol-seeking behavior, which may reflect differences in the value of drug-related stimuli.

Sex differences in reinstatement of cocaine-seeking with combination treatments of progesterone and atomoxetine

Two repurposed medications have been proposed to treat cocaine abuse. Progesterone, a gonadal hormone, and atomoxetine, a medication commonly used to treat attention deficit/hyperactivity disorder, have both been separately shown to reduce cocaine self-administration and reinstatement (i.e., relapse). The goal of the present study was to examine sex differences in the individual effects of PRO and ATO as well as the combination PRO+ATO treatment on cocaine (COC), caffeine (CAF), and/or cue-primed reinstatement of cocaine-seeking. Adult male and female Wistar rats lever-pressed under a FR 1 schedule for cocaine infusions (0.4mg/kg/inf). After 14 sessions of stable responding in daily 2-h sessions, rats underwent a 21-day extinction period when no drug or drug-related stimuli were present. Rats were then separated into four groups that received PRO (0.5mg/kg) alone (PRO+SAL), ATO (1.5mg/kg) alone (VEH+ATO), control (VEH+SAL) or combination (PRO+ATO) treatments prior to the reinstatement condition. Reinstatement of cocaine-seeking to cues and/or drug injections of cocaine or caffeine was tested after extinction. During maintenance, females self-administered more cocaine than males, but no sex differences were seen during extinction. Females showed greater cocaine-seeking than males after a CAF priming injection. Individual treatment with ATO did not decrease reinstatement under any priming condition; however, the combination treatment decreased cocaine-seeking under the COC+CUES priming condition in males, and both PRO alone and the combination treatment decreased cocaine-seeking in the CAF+CUES condition in females. Overall, PRO alone was only effective in reducing reinstatement in females, while the combination treatment was consistently effective in reducing reinstatement in both sexes.

Cue-induced craving to paraphernalia and drug images in opioid dependence.

Stimuli that are repeatedly paired with substance use, such as drug paraphernalia, can themselves elicit drug craving. The aim of this study was to examine whether particular cue types elicit greater craving responses than others among individuals with opioid dependence. Participants seeking inpatient treatment for opioid dependence were recruited for a study of cue-induced craving. This sample (N = 50), included 25 primary heroin users, 20 primary prescription opioid users, and 5 users of heroin and prescription opioids equally. Participants completed a cue reactivity task, in which images of drug-related stimuli were presented on a computer screen, each followed by a question assessing state drug craving. Overall, participants reported higher craving following paraphernalia stimuli relative to drug stimuli. However, this was moderated by opioid type; there was significantly higher craving in response to images of paraphernalia cues in the heroin group, and higher craving in response to drug cues in the prescription opioid group. These findings highlight potential differences in cue reactivity to opioid paraphernalia and drug cues, which appears to be moderated by drug type. Cue-induced craving is an important factor in relapse. This study adds further to the literature on cue-induced craving in opioid dependence, suggesting that craving may vary based on both cue type and opioid type. Future studies designed to discriminate the impact of substance of abuse, route of administration, and cue type will help to further clarify cue-induced craving in this population.

Cocaine addiction is associated with abnormal prefrontal function, increased striatal connectivity and sensitivity to monetary incentives, and decreased connectivity outside the human reward circuit.

Cocaine addiction has been associated with increased sensitivity of the human reward circuit to drug-related stimuli. However, the capacity of non-drug incentives to engage this network is poorly understood. Here, we characterized the functional sensitivity to monetary incentives and the structural integrity of the human reward circuit in abstinent cocaine-dependent (CD) patients and their matched controls. We assessed the BOLD response to monetary gains and losses in 30 CD patients and 30 healthy controls performing a lottery task in a magnetic resonance imaging scanner. We measured brain gray matter volume (GMV) using voxel-based morphometry and white matter microstructure using voxel-based fractional anisotropy (FA). Functional data showed that, after monetary incentives, CD patients exhibited higher activation in the ventral striatum than controls. Furthermore, we observed an inverted BOLD response pattern in the prefrontal cortex, with activity being highest after unexpected high gains and lowest after losses. Patients showed increased GMV in the caudate and the orbitofrontal cortex, increased white matter FA in the orbito-striatal pathway but decreased FA in antero-posterior association bundles. Abnormal activation in the prefrontal cortex correlated with GMV and FA increases in the orbitofrontal cortex. While functional abnormalities in the ventral striatum were inversely correlated with abstinence duration, structural alterations were not. In conclusion, results suggest abnormal incentive processing in CD patients with high salience for rewards and punishments in subcortical structures but diminished prefrontal control after adverse outcomes. They further suggest that hypertrophy and hyper-connectivity within the reward circuit, to the expense of connectivity outside this network, characterize cocaine addiction.

The role of attentional bias in obesity and addiction.

The purpose of this article is to critically evaluate the following claims derived from contemporary theoretical models of attentional bias (AB) for food- and drug-related stimuli: (a) AB is a characteristic feature of obesity and addiction, (b) AB predicts future behavior, (c) AB exerts a causal influence on consummatory behavior, and (d) AB reflects appetitive motivational processes. A focused discussion of the relevant literature is presented. The available evidence reveals inconsistencies with the aforementioned claims. Specifically, AB is not consistently associated with individual differences in body weight or drug use, AB does not consistently predict or influence distal consummatory behavior, and AB may be influenced by both appetitive and aversive motivational processes. These insights are synthesized into a theoretical account that claims that AB for food- and drug-related stimuli arises from momentary changes in evaluations of those stimuli that can be either positive (when the incentive value of the food or drug is high), negative (when individuals have a goal to change their behavior, and those stimuli are perceived as aversive), or both (when individuals experience motivational conflict, or ambivalence). The proposed theoretical synthesis may account for the contributions of appetitive and aversive motivational processes involved in self-regulatory conflicts to AB, and it yields testable predictions about the conditions under which AB should predict and have a causal influence on future consummatory behavior. This has implications for the prediction and modification of unhealthy behaviors and associated disorders. (PsycINFO Database Record

Chronic alcohol intake abolishes the relationship between dopamine synthesis capacity and learning signals in the ventral striatum.

Drugs of abuse elicit dopamine release in the ventral striatum, possibly biasing dopamine-driven reinforcement learning towards drug-related reward at the expense of non-drug-related reward. Indeed, in alcohol-dependent patients, reactivity in dopaminergic target areas is shifted from non-drug-related stimuli towards drug-related stimuli. Such 'hijacked' dopamine signals may impair flexible learning from non-drug-related rewards, and thus promote craving for the drug of abuse. Here, we used functional magnetic resonance imaging to measure ventral striatal activation by reward prediction errors (RPEs) during a probabilistic reversal learning task in recently detoxified alcohol-dependent patients and healthy controls (N = 27). All participants also underwent 6-[(18) F]fluoro-DOPA positron emission tomography to assess ventral striatal dopamine synthesis capacity. Neither ventral striatal activation by RPEs nor striatal dopamine synthesis capacity differed between groups. However, ventral striatal coding of RPEs correlated inversely with craving in patients. Furthermore, we found a negative correlation between ventral striatal coding of RPEs and dopamine synthesis capacity in healthy controls, but not in alcohol-dependent patients. Moderator analyses showed that the magnitude of the association between dopamine synthesis capacity and RPE coding depended on the amount of chronic, habitual alcohol intake. Despite the relatively small sample size, a power analysis supports the reported results. Using a multimodal imaging approach, this study suggests that dopaminergic modulation of neural learning signals is disrupted in alcohol dependence in proportion to long-term alcohol intake of patients. Alcohol intake may perpetuate itself by interfering with dopaminergic modulation of neural learning signals in the ventral striatum, thus increasing craving for habitual drug intake.

Changes in attentional bias to drug cues and fMRI Stroop with behavioral treatment for cocaine dependence

Changes in attentional bias to drug cues and fMRI Stroop with behavioral treatment for cocaine dependence

Is opioid dose a strong predictor of the risk of opioid overdose? Important confounding factors that change the dose–overdose relationship

Is opioid dose a strong predictor of the risk of opioid overdose? Important confounding factors that change the dose–overdose relationship

Competing neurobehavioral decision systems and the neuroeconomics of craving in opioid addiction

Competing neurobehavioral decision systems and the neuroeconomics of craving in opioid addiction Michael J Sofis,1 David P Jarmolowicz,1 Laura E Martin2 1University of Kansas, 2University of Kansas Medical Center, Lawrence, KS, USA Abstract: Craving is typically thought of as a classically conditioned response characterized by an elevated mesolimbic dopamine response to drug-related stimuli. Although this definition has spurred considerable research, the clinical impact of the research conducted has been less robust. The current review takes a more contemporary approach by conceptualizing craving as the breakdown of executive function and relative strengthening of the limbic system, occurring in the presence of conditioned cues, leading to a maladaptive craving response (ie, an increased likelihood of drug consumption). Working from this framework, the present review focuses on four issues in drug craving research: pivotal findings and limitations of cue-reactivity and neurocognitive tasks; two main processes of craving that include self-control and reward-based explanations; integration of neuroeconomic approaches to craving; and the theoretical implications and future directions of drug craving research. Keywords: craving, competing decision systems, executive function, loss of control, substance abuse