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Hypocretin/Orexin and Plastic Adaptations Associated with Drug Abuse

  • Corey Baimel
  • Stephanie L. Borgland
Chapter
Part of the Current Topics in Behavioral Neurosciences book series (CTBN, volume 33)

Abstract

Dopamine neurons in the ventral tegmental area (VTA) are a critical part of the neural circuits that underlie reward learning and motivation. Dopamine neurons send dense projections throughout the brain and recent observations suggest that both the intrinsic properties and the functional output of dopamine neurons are dependent on projection target and are subject to neuromodulatory influences. Lateral hypothalamic hypocretin (also termed orexin) neurons project to the VTA and contain both hypocretin and dynorphin peptides in the same dense core vesicles suggesting they may be co-released. Hypocretin peptides act at excitatory Gαq protein-coupled receptors and dynorphin acts at inhibitory Gαi/o protein-coupled receptors, which are both expressed on subpopulations of dopamine neurons. This review describes a role for neuromodulation of dopamine neurons and the influence on motivated behaviour in response to natural and drug rewards.

Keywords

AMPA Dopamine Hypocretin Morphine NMDA Ventral tegmental area 

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Authors and Affiliations

  1. 1.Department of Anesthesiology, Pharmacology and TherapeuticsUniversity of British ColumbiaVancouverCanada
  2. 2.Hotchkiss Brain InstituteUniversity of CalgaryCalgaryCanada

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