PT  - JOURNAL ARTICLE
AU  - Navarro, Gemma
AU  - Quiroz, César
AU  - Moreno-Delgado, David
AU  - Sierakowiak, Adam
AU  - McDowell, Kimberly
AU  - Moreno, Estefanía
AU  - Rea, William
AU  - Cai, Ning-Sheng
AU  - Aguinaga, David
AU  - Howell, Lesley A.
AU  - Hausch, Felix
AU  - Cortés, Antonio
AU  - Mallol, Josefa
AU  - Casadó, Vicent
AU  - Lluís, Carme
AU  - Canela, Enric I.
AU  - Ferré, Sergi
AU  - McCormick, Peter J.
TI  - Orexin–Corticotropin-Releasing Factor Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine
AID  - 10.1523/JNEUROSCI.4364-14.2015
DP  - 2015 Apr 29
TA  - The Journal of Neuroscience
PG  - 6639--6653
VI  - 35
IP  - 17
4099  - http://www.jneurosci.org/content/35/17/6639.short
4100  - http://www.jneurosci.org/content/35/17/6639.full
SO  - J. Neurosci.2015 Apr 29; 35
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.