Evidence for incentive salience sensitization as a pathway to alcohol use disorder

Cofresí, Roberto U.; Bartholow, Bruce D.; Piasecki, Thomas M.

doi:10.1016/j.neubiorev.2019.10.009

Cited by 67 publications

(76 citation statements)

References 672 publications

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“…Of note, high-stress conditions such as history of trauma, posttraumatic stress disorder (PTSD), low socio-economic status or poor social support are vulnerability factors for development of substance misuse and are frequently observed as comorbidities in opioid use disorder [5,23,51,52,94,103,113,131]. These findings align with prominent addiction theories pointing towards two major pathways into drug abuse, one related to drug liking and sensitization of the reward circuitry to drug related cues [25,101], and another more driven by attempts to reduce negative affective states and to cope with stressors [63].…”

Section: Introductionmentioning

confidence: 69%

The Role of Mu-Opioids for Reward and Threat Processing in Humans: Bridging the Gap from Preclinical to Clinical Opioid Drug Studies

2021

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Purpose of Review Opioid receptors are widely expressed in the human brain. A number of features commonly associated with drug use disorder, such as difficulties in emotional learning, emotion regulation and anhedonia, have been linked to endogenous opioid signalling. Whereas chronic substance use and misuse are thought to alter the function of the mu-opioid system, the specific mechanisms are not well understood. We argue that understanding exogenous and endogenous opioid effects in the healthy human brain is an essential foundation for bridging preclinical and clinical findings related to opioid misuse. Here, we will examine psychopharmacological evidence to outline the role of the mu-opioid receptor (MOR) system in the processing of threat and reward, and discuss how disruption of these processes by chronic opioid use might alter emotional learning and reward responsiveness. Recent Findings In healthy people, studies using opioid antagonist drugs indicate that the brain’s endogenous opioids downregulate fear reactivity and upregulate learning from safety. At the same time, endogenous opioids increase the liking of and motivation to engage with high reward value cues. Studies of acute opioid agonist effects indicate that with non-sedative doses, drugs such as morphine and buprenorphine can mimic endogenous opioid effects on liking and wanting. Disruption of endogenous opioid signalling due to prolonged opioid exposure is associated with some degree of anhedonia to non-drug rewards; however, new results leave open the possibility that this is not directly opioid-mediated. Summary The available human psychopharmacological evidence indicates that the healthy mu-opioid system contributes to the regulation of reward and threat processing. Overall, endogenous opioids can subtly increase liking and wanting responses to a wide variety of rewards, from sweet tastes to feelings of being connected to close others. For threat-related processing, human evidence suggests that endogenous opioids inhibit fear conditioning and reduce the sensitivity to aversive stimuli, although inconsistencies remain. The size of effects reported in healthy humans are however modest, clearly indicating that MORs play out their role in close concert with other neurotransmitter systems. Relevant candidate systems for future research include dopamine, serotonin and endocannabinoid signalling. Nevertheless, it is possible that endogenous opioid fine-tuning of reward and threat processing, when unbalanced by e.g. opioid misuse, could over time develop into symptoms associated with opioid use disorder, such as anhedonia and depression/anxiety.

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Section: Introductionmentioning

confidence: 69%

The Role of Mu-Opioids for Reward and Threat Processing in Humans: Bridging the Gap from Preclinical to Clinical Opioid Drug Studies

2021

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“…In humans with substance use disorders, drug-related cues are especially effective in capturing attention, and such cues can evoke craving and renewed drug use [73,74,75,76]. Such cue effects are especially evident during daily life outside the laboratory [77].…”

Section: Studies In Humansmentioning

confidence: 99%

Dopamine “Ups and Downs” in Addiction Revisited

Samaha¹,

Khoo²,

Ferrario³

et al. 2020

Preprint

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Drugs of abuse can change dopamine (DA) function during the development of addiction. But in what direction? By one view, drug use blunts DA neurotransmission, producing a hypodopaminergic state, and drug use is motivated to overcome DA deficiency. Another view is that drug use enhances DA neurotransmission, producing a sensitized, hyperdopaminergic reaction to drugs and drug cues, and continued drug use is motivated by sensitization of drug ‘wanting’. Here we discuss recent studies using intermittent cocaine self-administration procedures that mimic human patterns of use. These studies support the view that addiction-like behaviour involves sensitized DA responses to drugs and drug cues, consistent with human neuroimaging studies. These results have implications for modeling addiction in the laboratory, and for treatment.

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“…A limitation of the present study is that a random control group was not included for comparison. It has been established that paired CS-US presentations significantly increase sign tracking and ethanol consumption compared to the random controls (Tomie, et al, 2004 ), supporting the hypothesis that CS-triggered incentive salience sensitization (i.e., sign tracking) may contribute to the development of alcohol use disorder (Cofresí, Bartholow, & Piasecki, 2019 ; Tomie & Sharma, 2013 ). Nevertheless, sign tracking behavior does include associative and nonassociative components (e.g., influence of the intermittency of rewards) and the purpose of the present study was not to study associative learning per se but to investigate group differences in performance and changes in performance driven by the constraints of a sign tracking procedure.…”

Section: Discussionmentioning

confidence: 83%

Sign Tracking in an Enriched Environment: A Potential Ecologically Relevant Animal Model of Adaptive Behavior Change

Vigorito

López

Sisto

2021

Cogn Affect Behav Neurosci

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When an object conditioned stimulus (CS) is paired with a food unconditioned stimulus (US), anticipatory goal-directed action directed at the US location (goal tracking) is accompanied by behavior directed at the object CS (sign tracking). Sign-tracking behavior appears to be compulsive and habit-like and predicts increased vulnerability to the addictive potential of drugs in animal models. A large body of the literature also suggests that environmental enrichment protects against the development of addiction-prone phenotypes. Thus, we investigated whether compulsive-like sign tracking develops in environmentally enriched rats trained directly in their enriched home environment. We demonstrate that adolescent enriched-housed male Sprague-Dawley rats readily sign track a 5% ethanol bottle CS in their home environment and at a rate higher than adolescent standard-housed rats. We also show that enriched adolescent rats sign track less than enriched adult-trained rats and that acute isolation stress affects sign- and goal-tracking performance of adolescents and adults differently. Sign tracking increased more in the adult than the adolescent rats. Whereas the younger rats showed a decrease in goal tacking after the final stressor manipulation, the adults showed increased goal tracking. Our results are consistent with recent studies, which suggest that although sign tracking performance is compulsive-like, it is not as inflexible and habit-like as previously assumed. Testing in an enriched home environment with object CSs having greater affordance than “neutral” lever CSs may provide greater ecological relevance for investigating the development and expression of adaptive and compulsive-like behaviors in translational research.

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Evidence for incentive salience sensitization as a pathway to alcohol use disorder

Cited by 67 publications

References 672 publications

The Role of Mu-Opioids for Reward and Threat Processing in Humans: Bridging the Gap from Preclinical to Clinical Opioid Drug Studies

The Role of Mu-Opioids for Reward and Threat Processing in Humans: Bridging the Gap from Preclinical to Clinical Opioid Drug Studies

Dopamine “Ups and Downs” in Addiction Revisited

Sign Tracking in an Enriched Environment: A Potential Ecologically Relevant Animal Model of Adaptive Behavior Change

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