Abstract
Rationale
Existing data strongly suggest that alcohol affects dopamine (DA) neurotransmission in the brain. However, many questions remain about the effects of alcohol on the delicate equilibrium between such neurochemical processes as DA release and uptake. Dysregulation of these processes in the mesolimbic and nigrostriatal systems after chronic alcohol ingestion could be a neuroadaptation contributing to dependence.
Objectives
In the present study, we have employed an alcohol vapor inhalation model to characterize the effects of chronic alcohol exposure on DA dynamics in rat nucleus accumbens (NAc) and caudate putamen (CP) using fast-scan cyclic voltammetry (FSCV) in brain slices. This method provides a unique view of real-time, spatially resolved changes in DA concentration.
Results
We found that chronic alcohol exposure enhanced DA uptake rates in rat NAc and CP. These changes would have the effect of down-regulating extracellular DA levels, presumably a compensatory effect related to increased DA release by repeated alcohol exposure. The sensitivity of terminal release-regulating DA autoreceptors was not different in alcohol-exposed rats compared with alcohol-naïve animals.
Conclusions
The DA uptake changes after chronic alcohol exposure documented here using FSCV may be associated with a compensatory response of the DA system aimed at decreasing DA signaling. Alterations in autoreceptor function may require relatively long lasting alcohol exposure.
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Acknowledgements
The authors wish to thank Joanne Konstantopoulos for her contributions to the experiments and preparation of the manuscript. This work was supported by Wake Forest University School of Medicine Venture Funds, Alcoholic Beverage Medical Research Foundation (EAB) and National Institutes of Health Grants AA014686 (EAB), AA015830 (TAM), AA014091 and AA013900 (SRJ), AA014445 and AA015179 (BAM).
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Budygin, E.A., Oleson, E.B., Mathews, T.A. et al. Effects of chronic alcohol exposure on dopamine uptake in rat nucleus accumbens and caudate putamen. Psychopharmacology 193, 495–501 (2007). https://doi.org/10.1007/s00213-007-0812-1
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DOI: https://doi.org/10.1007/s00213-007-0812-1