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Nucleus accumbens fast-spiking interneurons in motivational and addictive behaviors

Molecular Psychiatry volume 26, pages 234–246 (2021)Cite this article

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Abstract

The development of drug addiction is associated with functional adaptations within the reward circuitry, within which the nucleus accumbens (NAc) is anatomically positioned as an interface between motivational salience and behavioral output. The functional output of NAc is profoundly altered after exposure to drugs of abuse, and some of the functional changes continue to evolve during drug abstinence, contributing to numerous emotional and motivational alterations related drug taking, seeking, and relapse. As in most brain regions, the functional output of NAc is critically dependent on the dynamic interaction between excitation and inhibition. One of the most prominent sources of inhibition within the NAc arises from fast-spiking interneurons (FSIs). Each NAc FSI innervates hundreds of principal neurons, and orchestrates population activity through its powerful and sustained feedforward inhibition. While the role of NAc FSIs in the context of drug addiction remains poorly understood, emerging evidence suggests that FSIs and FSI-mediated local circuits are key targets for drugs of abuse to tilt the functional output of NAc toward a motivational state favoring drug seeking and relapse. In this review, we discuss recent findings and our conceptualization about NAc FSI-mediated regulation of motivated and cocaine-induced behaviors. We hope that the conceptual framework proposed in this review may provide a useful guidance for ongoing and future studies to determine how FSIs influence the function of NAc and related reward circuits, ultimately leading to addictive behaviors.

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Fig. 1: Proposed role of NAc FSIs in regulating behavior.
Fig. 2: Long-term adaptations in the NAc FSI circuits induced by cocaine experience.

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Acknowledgements

The authors’ work was partially supported by NIH grants DA043940 (WJW), DA023206 (YD), DA047861 (YD), DA040620 (YD), and DA044538 (YD).

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  1. These authors contributed equally: Terra A. Schall, William J. Wright

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  1. Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Terra A. Schall & William J. Wright

  2. Departments of Neuroscience and Psychiatry, University of Pittsburgh, Pittsburgh, PA, 15260, USA

    Yan Dong

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Schall, T.A., Wright, W.J. & Dong, Y. Nucleus accumbens fast-spiking interneurons in motivational and addictive behaviors. Mol Psychiatry 26, 234–246 (2021). https://doi.org/10.1038/s41380-020-0683-y

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