Convergent actions of orexin/hypocretin and CRF on dopamine neurons: Emerging players in addiction.
The ventral tegmental area (VTA) is a brain region centrally involved in the development and expression of a variety of behaviors associated with drug use. Orexin/hypocretin (ox/hcrt) and corticotropin releasing factor (CRF) are both peptides released into the VTA, and an increasing number of studies show that both ox/hcrt and CRF in the VTA exert powerful modulatory effects on a variety of behaviors produced by drugs of abuse. Importantly, at a cellular and synaptic level, there is strong evidence supporting the hypothesis that these neuropeptides exert similar effects onto N-methyl-d-aspartate receptors (NMDARs) expressed in VTA neurons, suggesting a common molecular target in the actions of these peptides on this circuitry and ultimately on behaviors associated with drug use. In this review, we discuss emerging evidence that ox/hcrt and CRF directly target dopamine neurons by modulating excitatory synaptic activity, and that interaction of ox/hcrt and CRF may play a central role in addictive behaviors. Understanding these interactions in more detail may suggest new therapeutic targets in the treatment of relapse to substance abuse.
Borgland
Stephanie L
SL
Department of Anesthesiology, Pharmacology and Therapeutics, The University of British Columbia, Rm 212, 2176 Health Sciences Mall, Vancouver, BC, Canada V6T 1Z3.
Ungless
Mark A
MA
Bonci
Antonello
A
D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D000068797:Orexins; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism* / Q000503:physiopathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D003346:Corticotropin-Releasing Hormone