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Updated: Jul 12, 2025

Investigating Drivers of Antireward in Addiction Behavior with Anatomically Specific Single-Cell Gene Expression Methods
Published on: August 4, 2022
Restless legs syndrome, neuroleptic-induced akathisia, and opioid-withdrawal restlessness: shared neuronal
Sergi Ferré1, John W Winkelman2, Diego García-Borreguero3
1Integrative Neurobiology Section, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, MD, USA.
Abstract:
Restlessness is a core symptom underlying restless legs syndrome (RLS), neuroleptic-induced akathisia, and opioid withdrawal. These three conditions also share other clinical components suggesting some overlap in their pathophysiology. Recent prospective studies demonstrate the frequent incidence of RLS-like symptoms during opioid withdrawal and supervised prescription opioid tapering. Based on the therapeutic role of µ-opioid receptor (MOR) agonists in the three clinical conditions and recent preclinical experimental data in rodents, we provide a coherent and unifying neurobiological basis for the restlessness observed in these three clinical syndromes and propose a heuristic hypothesis of a key role of the specific striatal neurons that express MORs in akathisia/restlessness.
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