Oxytocin reduces methylphenidate-induced dorsal striatal dopamine release in male rhesus macaques

Mary R Lee; Ehsan Shokri Kojori; William Dieckmann; Erick Singley; Julie A Mattison; Peter Herscovitch; Lorenzo Leggio

doi:10.1093/ijnp/pyae056

Oxytocin reduces methylphenidate-induced dorsal striatal dopamine release in male rhesus macaques

Int J Neuropsychopharmacol. 2024 Nov 29:pyae056. doi: 10.1093/ijnp/pyae056. Online ahead of print.

Authors

Mary R Lee¹, Ehsan Shokri Kojori², William Dieckmann³, Erick Singley², Julie A Mattison⁴, Peter Herscovitch³, Lorenzo Leggio^{5

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Affiliations

¹ Veterans Affairs Medical Center, Washington DC, USA.
² National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Bethesda, MD, USA.
³ Positron Emission Tomography Department, National Institutes of Health Clinical Center, Bethesda, MD, USA.
⁴ Translational Gerontology Branch, National Institute on Aging, NIH Animal Center, Dickerson, MD, USA.
⁵ Clinical Psychoneuroendocrinology and Neuropsychopharmacology Section, Translational Addiction Medicine Branch, National Institute on Drug Abuse and National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Baltimore and Bethesda, Maryland, USA.
⁶ Medication Development Program, National Institute on Drug Abuse Intramural Research Program, National Institutes of Health, Baltimore, Maryland, USA.
⁷ Center for Alcohol and Addiction Studies, Department of Behavioral and Social Sciences, School of Public Health, Brown University, Providence, Rhode Island, USA.
⁸ Division of Addiction Medicine, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
⁹ Department of Neuroscience, Georgetown University Medical Center, Washington, DC, USA.

PMID: 39626021
DOI: 10.1093/ijnp/pyae056

Abstract

Background: Oxytocin is being evaluated as potential treatment for psychostimulant use disorders. It is unknown what effect oxytocin has on dopamine signaling in response to psychostimulants in brain regions such as the striatum where oxytocin and dopamine interact to process natural rewards. We investigated the effect of oxytocin on striatal dopamine release stimulated by methylphenidate whose mechanism of action is analogous to that of cocaine.

Method: We conducted an [11C] raclopride positron emission tomography study to assess striatal dopamine release in male rhesus macaques treated with oxytocin (80 IU) [administered via the intranasal (N=5) and intravenous (N=6) routes] followed by methylphenidate/[11C] raclopride.

Results: Oxytocin delivered by both routes significantly reduced methylphenidate-stimulated dopamine release in the dorsal striatum (caudate/putamen). These effects were, in part, evidenced by a reduction in dorsal striatal [11C] raclopride binding potential (increased dopamine release) following oxytocin administration.

Conclusion: The results provide translational and mechanistic evidence for the potential role of oxytocin as a treatment for psychostimulant use disorders.

Keywords: dopamine; intranasal; methylphenidate; oxytocin; raclopride.

Published by Oxford University Press on behalf of CINP 2024. This work is written by (a) US Government employee(s) and is in the public domain in the US.