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Influence of gut microbiome metabolites on cocaine demand and cocaine-seeking behavior

Neuropsychopharmacology volume 49, pages 357–358 (2024)Cite this article

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The resident bacteria of the gastrointestinal tract modulate the cellular and transcriptional activity of several brain cell types, which in turn affect various aspects of cognition and brain function. As a result, there is a great degree of speculation that aberrant gut-brain signaling may contribute to symptoms of neuropsychiatric disorders, including drug addiction [1]. The mechanisms by which gut-brain communication occurs are not fully understood, but may involve actions of metabolites secreted by gut microbiota, which enter systemic circulation and ultimately the brain. One potential class of such molecules are short-chain fatty acids (SFCAs, mainly propionate, butyrate, and acetate), which are produced by metabolic breakdown of dietary fiber.

In an earlier study, Kiraly et al. [2] reported that administration of non-absorbable antibiotics (Abx) to mice to deplete the gut microbiome increased locomotor sensitization to cocaine and cocaine-induced conditioned place preference. These effects were reversed by repletion of microbial SCFAs. To expand on these observations, Meckel et al. [3] now examined the effects of gut microbiome depletion with or without repletion of SFCAs on acquisition of and demand for intravenously self-administered cocaine, as well as cue-induced cocaine seeking after 3 weeks forced abstinence. Male Sprague-Dawley rats underwent depletion of the gut microbiome via administration of a mixture of the non-absorbable antibiotics neomycin, vancomycin, bacitracin and pimaricin in the drinking water for 2 weeks. Subsets of Abx-treated rats also received supplementation of SCFAs, and control rats received only SFCAs or water. Rats were food restricted (18 g/day) to increase motivation for operant responding, then underwent intravenous catheter implantation and tested for acquisition of self-administration of cocaine at a dose of 0.8 mg/kg/infusion in 3-h daily sessions across 7 days. Cue presentation accompanied each drug infusion. Microbiome depletion had no observable effects on acquisition of cocaine self-administration, nor did supplementation with SCFAs.

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Funding

Funding

The authors are supported by National Institutes of Health grants AA025590, AA030061, DA043172, and DA055153.

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  1. Department of Psychology and Interdisciplinary Graduate Program in Neuroscience, Arizona State University, Tempe, AZ, 85287, USA

    Amanda M. Acuña & M. Foster Olive

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  1. Amanda M. Acuña
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AMA and MFO reviewed the highlighted manuscript and wrote the commentary.

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Correspondence to M. Foster Olive.

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Acuña, A.M., Olive, M.F. Influence of gut microbiome metabolites on cocaine demand and cocaine-seeking behavior. Neuropsychopharmacol. 49, 357–358 (2024). https://doi.org/10.1038/s41386-023-01743-9

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