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Orexin-CRF Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine

Navarro, G, Moreno, D, Quiroz, C, Sierakowiak, A, McDowell, K, Rea, W, Cai, N-S, Moreno, E, Howell, L, Hausch, F, Cortés, A, Mallol, J, Casadó, V, Lluís, C, Canela, E, Ferre, S and McCormick, P (2015) Orexin-CRF Receptor Heteromers in the Ventral Tegmental Area as Targets for Cocaine Journal of Neuroscience, 35 (17). pp. 6639-6653.

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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.

Item Type: Article
Subjects : Veterinary Medicine
Authors :
NameEmailORCID
Navarro, GUNSPECIFIEDUNSPECIFIED
Moreno, DUNSPECIFIEDUNSPECIFIED
Quiroz, CUNSPECIFIEDUNSPECIFIED
Sierakowiak, AUNSPECIFIEDUNSPECIFIED
McDowell, KUNSPECIFIEDUNSPECIFIED
Rea, WUNSPECIFIEDUNSPECIFIED
Cai, N-SUNSPECIFIEDUNSPECIFIED
Moreno, EUNSPECIFIEDUNSPECIFIED
Howell, LUNSPECIFIEDUNSPECIFIED
Hausch, FUNSPECIFIEDUNSPECIFIED
Cortés, AUNSPECIFIEDUNSPECIFIED
Mallol, JUNSPECIFIEDUNSPECIFIED
Casadó, VUNSPECIFIEDUNSPECIFIED
Lluís, CUNSPECIFIEDUNSPECIFIED
Canela, EUNSPECIFIEDUNSPECIFIED
Ferre, SUNSPECIFIEDUNSPECIFIED
McCormick, Pp.mccormick@surrey.ac.ukUNSPECIFIED
Date : 29 April 2015
Identification Number : https://doi.org/10.1523/JNEUROSCI.4364-14.2015
Copyright Disclaimer : Copyright © 2015 the authors
Depositing User : Symplectic Elements
Date Deposited : 17 May 2017 10:46
Last Modified : 18 May 2017 12:43
URI: http://epubs.surrey.ac.uk/id/eprint/829146

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