Inhibiting subthalamic nucleus decreases cocaine demand and relapse: therapeutic potential

Brandon S. Bentzley, Gary Aston-Jones

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Preclinical evidence indicates that inactivation of subthalamic nucleus (STN) may be effective for treating cocaine addiction, and therapies that target STN, e.g. deep brain stimulation, are available indicating that this may have clinical promise. Here, we assessed the therapeutic potential of STN inactivation using a translationally relevant economic approach that quantitatively describes drug-taking behavior, and tested these results with drug-seeking tasks. Economic demand for cocaine was assessed in rats (n = 11) using a within-session threshold procedure in which cocaine price (responses/mg cocaine) was sequentially increased throughout the session. Cocaine demand was assessed in this manner immediately after bilateral microinfusions into STN of either vehicle (artificial cerebrospinal fluid) or the GABAA receptor agonist muscimol. A separate group of animals (n = 8) was tested for changes in cocaine seeking either during extinction or in response to cocaine-associated cues. Muscimol-induced inhibition of STN significantly attenuated cocaine consumption at high prices, drug seeking during extinction and cued reinstatement of cocaine seeking. In contrast, STN inhibition did not reduce cocaine consumption at low prices or locomotor activity. Thus, STN inactivation reduced economic demand for cocaine and multiple measures of drug seeking during extinction. In view of the association between economic demand and addiction severity in both rat and human, these results indicate that STN inactivation has substantial clinical potential for treatment of cocaine addiction.

Original languageEnglish (US)
Pages (from-to)946-957
Number of pages12
JournalAddiction Biology
Volume22
Issue number4
DOIs
StatePublished - Jul 2017

All Science Journal Classification (ASJC) codes

  • Medicine (miscellaneous)
  • Pharmacology
  • Psychiatry and Mental health

Keywords

  • addiction
  • behavioral economics
  • biomarker
  • cocaine
  • demand
  • subthalamic nucleus

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