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A microdialysis profile of β-endorphin and catecholamines in the rat nucleus accumbens following alcohol administration

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Abstract

Rationale

Alcohol stimulates the release of dopamine in the nucleus accumbens (NACB) of rats, mice and humans. There is evidence to suggest that the activation of beta-endorphin (β-EP) in the mesolimbic pathway by alcohol and other drugs of abuse may be associated with the rise in dopamine levels in the NACB.

Objectives

The present studies investigate whether the release of β-EP in the NACB is (1) dependent on the dose of alcohol that is administered, and (2) associated with changes in the extracellular concentrations of the catecholamines dopamine and norepinephrine, and the dopamine metabolites 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), in the NACB.

Methods

Male Sprague-Dawley rats were implanted with a microdialysis probe positioned in the shell region of the NACB. Artificial cerebrospinal fluid was pumped at a rate of 2.3 μl/min in awake and freely moving animals and the dialysate was collected at 30-min intervals. After a baseline period, rats were injected intraperitoneally with either physiological saline or one of three doses of alcohol: 0.8, 1.6, or 2.4 g ethanol/kg body weight. The dialysates collected were analyzed with radioimmunoassay, to estimate the content of β-EP; and high performance liquid chromatography, to estimate the content of dopamine, norepinephrine, DOPAC and HVA.

Results

Alcohol induced a dose-dependent increase in the extracellular levels of β-EP and dopamine. However, elevations in the extracellular levels of norepinephrine, DOPAC and HVA did not reach significance. The largest increase in β-EP and dopamine was observed with the 2.4 g/kg dose.

Conclusion

The alcohol-induced release of β-EP and dopamine in the NACB is dose-dependent, where the highest dose resulted in more pronounced concentrations in the dialysate. Furthermore, the increase in the extracellular levels of dopamine appeared to occur at an earlier time point following alcohol administration, than for β-EP. These results suggest that alcohol stimulates dopamine and β-EP in the NACB, but probably does so via independent mechanisms.

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Acknowledgements

These experiments were funded through a grant from the Natural Sciences and Engineering Research Council of Canada. Peter Marinelli is supported by a doctoral scholarship from Fonds de la recherche en santé du Québec.

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Authors and Affiliations

  1. Department of Neurology and Neurosurgery, Douglas Hospital Research Centre and McGill University, Montréal, Québec, Canada

    Peter W. Marinelli

  2. Departments of Psychiatry, Pharmacology and Therapeutics and Neurology and Neurosurgery, Douglas Hospital Research Centre and McGill University, Montréal, Québec, Canada

    Rémi Quirion

  3. Departments of Psychiatry and Physiology, Douglas Hospital Research Centre and McGill University, Montréal, Québec, Canada

    Christina Gianoulakis

  4. Douglas Hospital Research Centre, Lehmann Pavilion, 6875 LaSalle Boulevard, Verdun, Québec, Canada H4H 1R3

    Christina Gianoulakis

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  1. Peter W. Marinelli
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Correspondence to Christina Gianoulakis.

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Marinelli, P.W., Quirion, R. & Gianoulakis, C. A microdialysis profile of β-endorphin and catecholamines in the rat nucleus accumbens following alcohol administration. Psychopharmacology 169, 60–67 (2003). https://doi.org/10.1007/s00213-003-1490-2

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  • DOI: https://doi.org/10.1007/s00213-003-1490-2

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