Choline-Sigma-1R as an Additional Mechanism for Potentiation of Orexin by Cocaine

Authors

Jeffrey Barr, Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple University,Philadelphia, PA 19140, USA
Pingwei Zhao, Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple University,Philadelphia, PA 19140, USA
G Cristina Brailoiu, Department of Pharmaceutical Sciences, Thomas Jefferson University, Jefferson School of PharmacyFollow
Eugen Brailoiu, Center for Substance Abuse Research, Lewis Katz School of Medicine at Temple University,Philadelphia, PA 19140, USA

Document Type

Article

Publication Date

5-2-2021

Comments

This article is the author's final published version in International Journal of Molecular Sciences, Volume 22, Issue 10, 2 May 2021, Article number 5160.

The published version is available at https://doi.org/10.3390/ijms22105160

Copyright © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

his article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).

Abstract

Orexin A, an endogenous peptide involved in several functions including reward, acts via activation of orexin receptors OX₁ and OX₂, Gq-coupled GPCRs. We examined the effect of a selective OX₁ agonist, OXA (17-33) on cytosolic calcium concentration, [Ca²⁺ ]_i, in neurons of nucleus accumbens, an important area in the reward circuit. OXA (17-33) increased [Ca²⁺ ]_i in a dose-dependent manner; the effect was prevented by SB-334867, a selective OX₁ receptors antagonist. In Ca²⁺-free saline, the OXA (17-33)-induced increase in [Ca²⁺ ]_i was not affected by pretreatment with bafilomycin A1, an endo-lysosomal calcium disrupter, but was blocked by 2-APB and xestospongin C, antagonists of inositol-1,4,5-trisphosphate (IP₃ ) receptors. Pretreatment with VU0155056, PLD inhibitor, or BD-1047 and NE-100, Sigma-1R antagonists, reduced the [Ca²⁺ ]_i response elicited by OXA (17-33). Cocaine potentiated the increase in [Ca²⁺ ]_i by OXA (17-33); the potentiation was abolished by Sigma-1R antagonists. Our results support an additional signaling mechanism for orexin A-OX₁ via choline-Sigma-1R and a critical role for Sigma-1R in the cocaine–orexin A interaction in nucleus accumbens neurons.

Recommended Citation

Barr, Jeffrey; Zhao, Pingwei; Brailoiu, G Cristina; and Brailoiu, Eugen, "Choline-Sigma-1R as an Additional Mechanism for Potentiation of Orexin by Cocaine" (2021). Department of Pharmacology and Experimental Therapeutics Faculty Papers. Paper 129.
https://jdc.jefferson.edu/petfp/129

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 License.

Language

English