# name
Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine

# metadata.dc.contributor.author[].value
Canela Campos, Enric I. (Enric Isidre), 1949-

# metadata.dc.description.abstract[].value
Release of the neuropeptides corticotropin-releasing factor (CRF) and orexin-A in the ventral tegmental area (VTA) play an important role in stress-induced cocaine-seeking behavior. We provide evidence for pharmacologically significant interactions between CRF and orexin-A that depend on oligomerization of CRF1 receptor (CRF1R) and orexin OX1 receptors (OX1R). CRF1R-OX1R heteromers are the conduits of a negative crosstalk between orexin-A and CRF as demonstrated in transfected cells and rat VTA, in which they significantly modulate dendritic dopamine release. The cocaine target sigma1 receptor (sigma1R) also associates with the CRF1R-OX1R heteromer. Cocaine binding to the sigma1R-CRF1R-OX1R complex promotes a long-term disruption of the orexin-A-CRF negative crosstalk. Through this mechanism, cocaine sensitizes VTA cells to the excitatory effects of both CRF and orexin-A, thus providing a mechanism by which stress induces cocaine seeking.

# metadata.dc.rights[].value
cc-by-nc-sa (c) Navarro Brugal, Gemma et al., 2015

# metadata.dc.source[].value
Articles publicats en revistes (Bioquímica i Biomedicina Molecular)

# metadata.dc.title[].value
Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine