Chronic alcohol exposure disrupts top-down control over basal ganglia action selection to produce habits

Renteria, Rafael; Baltz, Emily T; Gremel, Christina M.

doi:10.1038/s41467-017-02615-9

Cited by 152 publications

(177 citation statements)

References 72 publications

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“…The rostral part of the ACC is implicated in error-related responses, including affective processing, and the caudal part of the ACC is associated with detection of conflict to recruit cognitive control 53 . Thus, reduction in inputs from prefrontal and cingulate cortices into striatum may disrupt the control over action selection 54 .…”

Section: Primary Outcome: Altered Brain Morphometry In Sudsmentioning

confidence: 99%

Gray and white matter morphology in substance use disorders: A neuroimaging systematic review and meta-analysis

Pando‐Naude

Toxto

Fernandez‐Lozano

et al. 2020

Preprint

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Substance use disorders (SUDs) are characterized by a compulsion to seek and consume one or more substances of abuse, with a perceived loss of control and negative emotional state. Repeated use of a substance results in synaptic and morphological changes, secondary to toxicity and SUD pathology in the dopamine striato-thalamo-cortical and limbic pathways. These neuroadaptations seem to vary between studies, which could be related to divergent effects of substances, consumption severity or other unknown factors. We therefore identified studies investigating the effects of SUDs using volumetric whole-brain voxel-based morphometry (VBM) in gray (GM) and white matter (WM). We performed a systematic review and meta-analysis of VBM studies using the anatomic likelihood estimation (ALE) method implemented in GingerALE (PROSPERO pre-registration CRD42017071222). Fifty studies met inclusion criteria and were included in the final quantitative meta-analysis, with a total of 538 foci, 88 experiments and 4370 participants. We found convergence and divergence in brain regions and volume effects (higher vs lower volume) in GM and WM depending on the severity of consumption pattern and type of substance. Convergent pathology was evident across substances in GM of the insula, anterior cingulate cortex, putamen, and thalamus, and in WM of the thalamic radiation and internal capsule bundle. Divergent pathology between occasional use (cortical pathology) and addiction (cortical-subcortical pathology) provides evidence of a possible top-down neuroadaptation. Our findings indicate distinctive brain morphometry alterations in SUDs, which may inform our understanding of disease progression and ultimately therapeutic approaches.MANUSCRIPT Pando-Naude, Victor Garza-Villarreal, Eduardo A.MANUSCRIPT Pando-Naude, Victor Garza-Villarreal, Eduardo A. 5 terms for articles published to the end of July 2018. No restrictions were placed on study design, but in order to be eligible for inclusion, the studies must have reported whole-brain VBM analyses. Screening and data extraction were performed using the Covidence tool 31 . The main outcome to extract was any change in gray and/or white matter analyzed using VBM, in stereotactic coordinates, comparing a substance user group and a healthy control group (details in Supplementary information). Quality assessment of MRI studies.Criteria for MRI quality reporting was selected from a set of guidelines for the standardized reporting of MRI studies [32][33][34] . Such guidelines dictate a more consistent and coherent policy for the reporting of MRI methods to ensure that methods can be understood and replicated. Analysis and meta-analytic technique.Statistically significant foci from between-group contrasts were extracted and recorded for each study. If necessary, coordinates were converted from Talairach coordinates to MNI space using the Lancaster transform (icbm2tal) incorporated in GingerALE (www.brainmap.org/). All metaanalyses were performed using anatomic likelihood estimation (ALE), implemented ...

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Section: Primary Outcome: Altered Brain Morphometry In Sudsmentioning

confidence: 99%

Gray and white matter morphology in substance use disorders: A neuroimaging systematic review and meta-analysis

Pando‐Naude

Toxto

Fernandez‐Lozano

et al. 2020

Preprint

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“…A transition from goal‐directed to habitual responding for drugs of abuse is thought to contribute to the compulsive patterns of drug‐seeking and taking that are characteristic of SUD (Barker & Taylor, ; Everitt & Robbins, ; Jentsch & Taylor, ; Ostlund & Balleine, ). Exposure to drugs of abuse including amphetamine, alcohol, or cannabis can engender faster formation of habits (Nazzaro et al., ; Nelson & Killcross, ; Renteria, Baltz, & Gremel, ). Identification of pharmacological tools that are able to reduce habitual and subsequently improve goal‐directed control of behavior would, therefore have substantial therapeutic benefit for disorders in which compulsive, habitual actions are a primary deficit.…”

Section: Introductionmentioning

confidence: 99%

Bi‐directional modulation of food habit expression by the endocannabinoid system

Gianessi

Groman

Taylor

2019

Eur J of Neuroscience

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The compulsive, habitual behaviors that have been observed in individuals diagnosed with substance use disorders may be due to disruptions in the neural circuits that mediate goal‐directed actions. The endocannabinoid system has been shown to play a critical role in habit learning, but the role of this neuromodulatory system in habit expression is unclear. Here, we investigated the role of the endocannabinoid system in established habitual actions using contingency degradation in male C57BL/6 mice. We found that administration of the endocannabinoid transport inhibitor AM404 reduced habitual responding for food and that antagonism of cannabinoid receptor type 1 (CB1), but not transient receptor potential cation subfamily V (TRPV1), receptors produced a similar reduction in habitual responding. Moreover, pharmacological stimulation of CB1 receptors increased habitual responding for food. Co‐administration of an enzyme inhibitor that selectively increases the endocannabinoid 2‐arachidonoyl glycerol (2‐AG) with AM404 partially restored habitual responding for food. Together, these findings demonstrate an important role for the endocannabinoid system in the expression of habits and provide novel insights into potential pharmacological strategies for reducing habitual behaviors in mental disorders.

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“…After 7 weeks of intermittent access to 20% alcohol using a 2 bottle choice paradigm (IA20%2BC), high-drinking rats (alcohol intake >3.5 g/kg/24h) were trained to self-administer 20% alcohol in an operant self-administration (OSA) paradigm (34) with modification adapted from (20, 35,36).…”

Section: Habitual and Goal-directed Alcohol Seekingmentioning

confidence: 99%

“…The OFC sends projections to the dorsal striatum (DS), including the DLS (20). In addition, Renteria and colleagues showed that alcohol vapor exposure generated habitual behavior via the disruption of OFC to DMS circuit (36). Thus, it is plausible that mTORC1 activation is strengthening OFC projections to the DLS and or through weakening of OFC to DMS projection.…”

Section: Mtorc1 In the Ofc And Habitmentioning

confidence: 99%

mTORC1 In the Orbitofrontal Cortex Promotes Habitual Alcohol Seeking

Morisot

Phamluong

Ehinger

et al. 2019

Preprint

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25The mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in 26 dendritic translation and in learning and memory. We previously showed that heavy 27 alcohol use activates mTORC1 in the orbitofrontal cortex (OFC) of rodents (1). Here, we 28 set out to determine the consequences of alcohol-dependent mTORC1 activation in the 29 OFC. We found that inhibition of mTORC1 activity attenuates alcohol seeking and restores 30 sensitivity to outcome devaluation in rats that habitually seek alcohol. In contrast, habitual 31 responding for sucrose was unaltered by mTORC1 inhibition, suggesting that mTORC1's 32 role in habitual behavior is specific to alcohol. We further show that inhibition of GluN2B 33 in the OFC attenuates alcohol-dependent mTORC1 activation, alcohol seeking and 34 habitual responding for alcohol. Together, these data suggest that the GluN2B/mTORC1 35 axis in the OFC drives alcohol seeking and habit. 36 37 38 39 40 41 42 43 44 45 46 47 48 49mTORC1 is a multiprotein complex that contains the serine/threonine protein 50 kinase mTOR, the regulatory associated protein of TOR (Raptor), and other enzymes and 51 adaptor proteins (2). Upon activation, mTORC1 phosphorylates eIF4E-binding protein 52 (4E-BP) and the ribosomal protein S6 kinase (S6K), which in turn phosphorylates its 53 substrate, S6 (3). These phosphorylation events lead to the translation of a subset of 54 mRNAs to proteins (2, 3). In the CNS, mTORC1 is responsible for the local dendritic 55 translation of synaptic proteins (4, 5). As such, mTORC1 plays an important role in 56 synaptic plasticity, and learning and memory (6). 57Increasing lines of evidence in rodents suggest that mTORC1 is a key player in 58 mechanisms underlying alcohol use disorder (AUD) (7). For instance, excessive alcohol 59 intake and reinstatement of alcohol place preference activate mTORC1 in the rodent 60 nucleus accumbens (NAc) (1, 8-10), resulting in the translation of synaptic proteins, which 61 in turn produce synaptic and structural adaptations that drive and maintain heavy alcohol 62 use and relapse (1, 8, 9, 11, 12). Repeated cycles of voluntary binge drinking of alcohol 63 and withdrawal also produces a robust and sustained activation of mTORC1 in the OFC of 64 rodents (1); however, the behavioral consequences of this activation are unknown. 65The OFC integrates sensory and reward information (13) and is an essential player 66 in decision making (13-15), in stimulus-outcome association (16-18), in updating the value 67 of predicted outcomes (15, 19), in goal-directed behaviors (16, 20, 21), and in compulsive 68 behavior (22, 23). Exposure to drugs of abuse impairs the performance of OFC-dependent 69 behavioral tasks (24), and aberrant neuroadaptations induced by drugs of abuse in the OFC 70 contribute to drug-seeking and compulsive drug taking (24-26). For example, withdrawal 71 from alcohol vapor exposure produces morphological and cellular alterations in rodents 72 4 (27, 28). Inactivation of the OFC enhances alcohol consumption in alcohol-depe...

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Chronic alcohol exposure disrupts top-down control over basal ganglia action selection to produce habits

Cited by 152 publications

References 72 publications

Gray and white matter morphology in substance use disorders: A neuroimaging systematic review and meta-analysis

Gray and white matter morphology in substance use disorders: A neuroimaging systematic review and meta-analysis

Bi‐directional modulation of food habit expression by the endocannabinoid system

mTORC1 In the Orbitofrontal Cortex Promotes Habitual Alcohol Seeking

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