Exploring the consequences of social defeat stress and intermittent ethanol drinking on dopamine dynamics in the rat nucleus accumbens

Alex L Deal,Joanne K Konstantopoulos,Evgeny A Budygin,Jeff L Weiner

doi:10.1038/s41598-017-18706-y

Alex L Deal, Joanne K Konstantopoulos + Show 2 more

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https://doi.org/10.1038/s41598-017-18706-y

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Abstract

The current study aimed to explore how presynaptic dopamine (DA) function is altered following brief stress episodes and chronic ethanol self-administration and whether these neuroadaptations modify the acute effects of ethanol on DA dynamics. We used fast-scan cyclic voltammetry to evaluate changes in DA release and uptake parameters in rat nucleus accumbens brain slices by analyzing DA transients evoked through single pulse electrical stimulation. Adult male rats were divided into four groups: ethanol-naïve or ethanol drinking (six week intermittent two-bottle choice) and stressed (mild social defeat) or nonstressed. Results revealed that the mild stress significantly increased DA release and uptake in ethanol-naïve subjects, compared to nonstressed controls. Chronic ethanol self-administration increased the DA uptake rate and occluded the effects of stress on DA release dynamics. Bath-applied ethanol decreased stimulated DA efflux in a concentration-dependent manner in all groups; however, the magnitude of this effect was blunted by either stress or chronic ethanol, or by a combination of both procedures. Together, these findings suggest that stress and ethanol drinking may promote similar adaptive changes in accumbal presynaptic DA release measures and that these changes may contribute to the escalation in ethanol intake that occurs during the development of alcohol use disorder.

Highlights

It is well known that a wide range of stressful events can effectively trigger alcohol drinking behaviors in humans[1,2,3]
We found that a history of moderate ethanol self-administration through the two-bottle choice paradigm significantly increased the rate of DA uptake and that this drinking experience blunted the effects of social defeat stress on accumbal DA dynamics
We demonstrated that stress and ethanol self-administration decreased the acute effects of ethanol on evoked DA efflux in the nucleus accumbens and that ethanol drinking occluded additional effects of stress on this measure

Summary

Introduction

It is well known that a wide range of stressful events can effectively trigger alcohol drinking behaviors in humans[1,2,3]. Ex vivo neurochemical studies have reported that both contingent and non-contingent chronic ethanol exposure[16,17,18,19] as well as early-life social isolation stress[9,20] trigger increases in dopamine (DA) reuptake rate in striatal subregions, including the nucleus accumbens This outcome may result (at least in part) in a functional deficit in tonic DA release. This study sought to determine if a history of ethanol self-administration influenced any DA neuroadaptations induced by social defeat stress or if either procedure altered the acute effects of ethanol on accumbal DA release These questions were addressed using fast-scan cyclic voltammetry (FSCV) coupled with single pulse electrical stimulation to evaluate changes in DA release and uptake parameters in the rat nucleus accumbens. These measures were performed on brain slices obtained from rats that were ethanol-naïve or chronically exposed to an intermittent home-cage ethanol drinking regimen and subsequently exposed or not exposed to stress (social defeat)

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