Elsevier

Drug and Alcohol Dependence

Volume 207, 1 February 2020, 107811
Drug and Alcohol Dependence

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Acute alcohol intake alters resting state functional connectivity of nucleus accumbens with pain-related corticolimbic structures

https://doi.org/10.1016/j.drugalcdep.2019.107811Get rights and content

Highlights

  • Growing evidence suggests common neural underpinnings of pain and alcohol effects.

  • Alcohol intake reduced functional connectivity between mesocorticolimbic regions.

  • Collectively, these regions underlie reward, motivated behavior, and pain response.

Abstract

Background

The nucleus accumbens (NAc) is a ventral striatal structure underlying reward, reinforcement, and motivation, with extensive anatomic and functional connections to a wide range of affective processing structures (medial prefrontal cortex (mPFC), amygdala, and insula). Characterizing how acute alcohol intake affects resting state functional connectivity (rsFC) between the nucleus accumbens (NAc) and these regions will improve mechanistic understanding of alcohol’s neurobehavioral effects, including the neural overlap between acute alcohol effects and pain processing.

Methods

Fifteen healthy social drinkers (10 women; age: 25–45 years) were included in the study. Participants completed one session in which they consumed an alcohol dose targeting a breath alcohol concentration of 0.08 g/dL, and in a second a placebo beverage. Nine-minute resting state fMRI scans were acquired 30−35 min after beverage administration during each session. rsFC between NAc and a priori corticolimbic regions of interest (mPFC, amgydala, and insula), were compared between beverage conditions. We also conducted an exploratory whole-brain seed-to-voxel analysis of NAc FC.

Results

Alcohol intake reduced rsFC between NAc and mPFC, as well as NAc and amygdala. Alcohol also reduced rsFC between NAc and a 97-voxel cluster including bilateral paracingulate cortex and anterior cingulate cortex.

Conclusions

Findings suggest that acute alcohol intake reduces rsFC between NAc and several structures, including mPFC, amygdala, and rostral ACC in healthy social drinkers. These structures underlie reward, motivated behavior, and emotion regulation, and may provide mechanistic insight to how alcohol affects related processes, including pain.

Introduction

The nucleus accumbens (NAc) is a basal forebrain structure with neuroanatomic and functional connections to a range of structures, including medial prefrontal cortex (mPFC), amygdala, and insula (Ikemoto, 2010).The role of the NAc in reinforcement and reward associated with alcohol use is well appreciated (Russo et al., 2010); briefly, alcohol-induced release of dopamine and opioid peptides in the NAc underlie its reinforcing properties (Koob and Volkow, 2010). Chronic pain and alcohol use disorder (AUD) frequently co-occur (e.g., Boissoneault et al., 2019) and involve overlapping neural substrates (Apkarian et al., 2013; Becerra and Borsook, 2008; Egli et al., 2012; Scott et al., 2006; Zale et al., 2015), but empirical studies regarding alcohol effects on resting state functional connectivity (rsFC) between regions and networks relevant to alcohol/pain interactions, including NAc, are lacking.

Previous studies have examined changes in rsFC with acute alcohol administration (e.g., Gorka et al., 2018; Shokri-Kojori et al., 2017). However, acute alcohol effects on NAc-related circuits underlying motivation/reward, pain processing and chronification have not previously been examined. Thus, this study examined the acute effects of alcohol on rsFC between NAc and mPFC. Because alcohol can have analgesic effects in experimental settings (Thompson et al., 2017), and chronic pain is associated with greater rsFC between these structures, we hypothesized that acute alcohol intake would reduce NAc-mPFC connectivity. We also examined alcohol effects on connectivity of NAc with amygdala and insula, given their extensive anatomic and functional connections to the NAc (Ikemoto, 2010) and their role in modulating both alcohol’s reinforcing effects and the pain experience (Koob and Volkow, 2010).

Section snippets

Participants

Community-dwelling healthy drinkers (N = 15; 10 women), 25–45 years of age, were recruited as part of a study regarding biopsychosocial mechanisms underlying alcohol analgesia. Informed consent was obtained prior to data collection. The study was approved by the University of Florida IRB (Protocol #2018-0889).

Screening procedure

During the screening/eligibility session, participants completed questionnaires (demographics; medical history; Beck Depression Inventory-II (BDI-II; Beck et al., 1996); State-Trait

Participant characteristics

Participants averaged 30.8 years of age (SD = 3.7) and 20.1 years of education (SD = 2.87). Mean BDI-II and STAI-trait scores were 3.27 (SD = 3.8) and 29.3 (SD = 7.4), indicating minimal distress. Participants consumed, on average, 0.63 (SD = .37) oz. absolute ethanol/day over the 6 months prior to screening (∼1 standard drink). Maximum single-day consumption during this period averaged 4.68 (SD = 2.05) oz. absolute ethanol (∼8 standard drinks). The mean AUDIT score was 5.1 (SD = 1.8).

BrAC and SAC measures

Mean BrAC

Discussion

Results supported hypotheses that acute alcohol would disrupt NAc-mPFC and NAc-amygdala rsFC. Whole-brain analyses also indicated alcohol-related disruption of NAc-paracingulate/ACC rsFC. Alcohol did not appear to meaningfully affect NAc-insula rsFC.

Alcohol-related reductions in NAc-mPFC connectivity are intriguing given evidence that greater rsFC between these structures is associated with poorer self-regulation of experimental pain (Woo et al., 2015), chronic pain status (Baliki et al., 2010

Contributors

JB and MR designed the study, JB and BS collected data, JB conducted analyses, and JB, BS, and MR wrote the manuscript. All authors approved the final version of the manuscript for submission.

Role of funding source

Support for this work was provided by the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under award number R01AA025337. The content of this article is solely the responsibility of the authors and does not necessarily represent the official view of the National Institutes of Health.

Declaration of Competing Interest

The authors declare no conflict of interest.

Acknowledgment

The authors wish to thank the participants of this study for their willingness to participate.

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