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Oral alprazolam acutely increases nucleus accumbens perfusion

Molecular Psychiatry volume 18, pages 960–961 (2013)Cite this article

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Benzodiazepines treat anxiety, but can also produce euphoric effects, contributing to abuse. Using perfusion magnetic resonance imaging, we provide the first direct evidence in humans that alprazolam (Xanax) acutely increases perfusion in the nucleus accumbens, a key reward-processing region linked to addiction.

Benzodiazepines exert not only therapeutic anxiolytic effects but also undesirable side effects by enhancing GABA signaling through receptors expressed widely in the brain. Benzodiazepine receptors are enriched in human ventral striatum/nucleus accumbens,1 a critical region for normal and pathological motivational processes. Recent non-human studies demonstrated that benzodiazepines activate accumbens through alpha-1 GABA receptor-mediated disinhibition of mesolimbic dopamine projections to accumbens,2 as well as through direct effects on alpha-2 GABA receptors.3 However, there is no direct evidence of benzodiazepine effects on accumbens in humans.

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Acknowledgements

This study was funded by AstraZeneca Pharmaceuticals LP. Dr Wolf was also supported by NIMH K23MH085096, APIRE, and the Sidney R Baer, Jr Foundation through the Brain & Behavior Research Foundation. Dr Satterthwaite was supported by NIMH K23MH098130 and the Marc Rapport Family Investigator grant through the Brain & Behavior Research Foundation.

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Author notes

  1. A E Pinkham

    Present address: 6Current address: Department of Psychology, Southern Methodist University, Dallas, TX 75275, USA.,

Authors and Affiliations

  1. Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    D H Wolf, A E Pinkham, T D Satterthwaite, K Ruparel, J Valdez, R C Gur & R E Gur

  2. Department of Radiology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    M A Elliott, J A Detre, R C Gur & R E Gur

  3. AstraZeneca Pharmaceuticals LP, Wilmington, DE, USA

    M A Smith

  4. Department of Neurology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA

    J A Detre, R C Gur & R E Gur

  5. The Philadelphia Veterans Administration Medical Center, Philadelphia, PA, USA

    R C Gur

Authors
  1. D H Wolf
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  2. A E Pinkham
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  3. T D Satterthwaite
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Corresponding author

Correspondence to D H Wolf.

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Competing interests

Dr MA Smith is an employee of AstraZeneca Pharmaceuticals, the study sponsor. Dr RC Gur and Dr RE Gur report research funding from AstraZeneca and Pfizer. The other authors have no conflict of interest.

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Wolf, D., Pinkham, A., Satterthwaite, T. et al. Oral alprazolam acutely increases nucleus accumbens perfusion. Mol Psychiatry 18, 960–961 (2013). https://doi.org/10.1038/mp.2012.139

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