title: High-Frequency Stimulation of the Subthalamic Nucleus Blocks Compulsive-Like Re-Escalation of Heroin Taking in Rats.
abstract: Opioid addiction, including addiction to heroin, has markedly increased in the past decade. The cost and pervasiveness of heroin addiction, including resistance to recovery from addiction, provide a compelling basis for developing novel therapeutic strategies. Deep brain stimulation may represent a viable alternative strategy for the treatment of intractable heroin addiction, particularly in individuals who are resistant to traditional therapies. Here we provide preclinical evidence of the therapeutic potential of high-frequency stimulation of the subthalamic nucleus (STN HFS) for heroin addiction. STN HFS prevented the re-escalation of heroin intake after abstinence in rats with extended access to heroin, an animal model of compulsive heroin taking. STN HFS inhibited key brain regions, including the substantia nigra, entopeduncular nucleus, and nucleus accumbens shell measured using brain mapping analyses of immediate-early gene expression and produced a robust silencing of STN neurons as measured using whole-cell recording ex vivo. These results warrant further investigation to examine the therapeutic effects that STN HFS may have on relapse in humans with heroin addiction.
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Carrie L
authors.initials: CL
authors.lastname: Wade
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Marsida
authors.initials: M
authors.lastname: Kallupi
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Daniel O
authors.initials: DO
authors.lastname: Hernandez
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.|CNRS and Aix Marseille Université, INT UMR7289, Marseille, France.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Breysse
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Giordano
authors.initials: G
authors.lastname: de Guglielmo
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Crawford
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: George F
authors.initials: GF
authors.lastname: Koob
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Schweitzer
authors.affiliation: CNRS and Aix Marseille Université, INT UMR7289, Marseille, France.
authors.forename: Christelle
authors.initials: C
authors.lastname: Baunez
authors.affiliation: Committee on the Neurobiology of Addictive Disorders, The Scripps Research Institute, La Jolla, CA, USA.
authors.forename: Olivier
authors.identifier: http://orcid.org/0000-0002-3700-5003
authors.initials: O
authors.lastname: George
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage; D000818:Animals; D003192:Compulsive Behavior / Q000503:physiopathology* / Q000628:therapy*; D046690:Deep Brain Stimulation; D004195:Disease Models, Animal; D058999:Drug-Seeking Behavior / Q000502:physiology; D003932:Heroin / Q000008:administration & dosage; D006556:Heroin Dependence / Q000503:physiopathology* / Q000628:therapy*; D008297:Male; D008564:Membrane Potentials / Q000502:physiology; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D017208:Rats, Wistar; D012646:Self Administration; D020531:Subthalamic Nucleus / Q000503:physiopathology*; D046509:Tissue Culture Techniques
chemical_list: D000701:Analgesics, Opioid; D016760:Proto-Oncogene Proteins c-fos; D003932:Heroin