RT Journal Article
SR Electronic
T1 Orexin–Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6639
OP 6653
DO 10.1523/JNEUROSCI.4364-14.2015
VO 35
IS 17
A1 Navarro, Gemma
A1 Quiroz, César
A1 Moreno-Delgado, David
A1 Sierakowiak, Adam
A1 McDowell, Kimberly
A1 Moreno, Estefanía
A1 Rea, William
A1 Cai, Ning-Sheng
A1 Aguinaga, David
A1 Howell, Lesley A.
A1 Hausch, Felix
A1 Cortés, Antonio
A1 Mallol, Josefa
A1 Casadó, Vicent
A1 Lluís, Carme
A1 Canela, Enric I.
A1 Ferré, Sergi
A1 McCormick, Peter J.
YR 2015
UL http://www.jneurosci.org/content/35/17/6639.abstract
AB 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 σ1 receptor (σ1R) also associates with the CRF1R–OX1R heteromer. Cocaine binding to the σ1R–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.