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Updated: Apr 13, 2026

A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder
Published on: June 18, 2018
Orexin-corticotropin-releasing factor receptor heteromers in the ventral tegmental area as targets for cocaine
Gemma Navarro1, César Quiroz2, David Moreno-Delgado1
1Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Barcelona, Center for Biomedical Research in Neurodegenerative Diseases Network and Institute of Biomedicine of the University of Barcelona, 08028 Barcelona, Spain.
Abstract:
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.
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