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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.
AuthorsCarrie L Wade, Marsida Kallupi, Daniel O Hernandez, Emmanuel Breysse, Giordano de Guglielmo, Elena Crawford, George F Koob, Paul Schweitzer, Christelle Baunez, Olivier George
JournalNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 42 Issue 9 Pg. 1850-1859 (Aug 2017) ISSN: 1740-634X [Electronic] England
PMID27917870 (Publication Type: Journal Article)
Chemical References
  • Analgesics, Opioid
  • Proto-Oncogene Proteins c-fos
  • Heroin
Topics
  • Analgesics, Opioid (administration & dosage)
  • Animals
  • Compulsive Behavior (physiopathology, therapy)
  • Deep Brain Stimulation
  • Disease Models, Animal
  • Drug-Seeking Behavior (physiology)
  • Heroin (administration & dosage)
  • Heroin Dependence (physiopathology, therapy)
  • Male
  • Membrane Potentials (physiology)
  • Proto-Oncogene Proteins c-fos (metabolism)
  • Rats, Wistar
  • Self Administration
  • Subthalamic Nucleus (physiopathology)
  • Tissue Culture Techniques

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