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 (C) 2009 Elsevier B.V. All rights reserved.