Orexin-1 receptor signaling increases motivation for cocaine-associated cues

The European Journal of Neuroscience
Brandon S Bentzley, Gary Aston-Jones

Abstract

The orexin/hypocretin system is involved in multiple cocaine addiction processes that involve drug-associated environmental cues, including cue-induced reinstatement of extinguished cocaine seeking and expression of conditioned place preference. However, the orexin system does not play a role in several behaviors that are less cue-dependent, such as cocaine-primed reinstatement of extinguished cocaine seeking and low-effort cocaine self-administration. We hypothesized that cocaine-associated cues, but not cocaine alone, engage signaling at orexin-1 receptors (OX1Rs), and this cue-engaged OX1R signaling increases motivation for cocaine. Motivation for cocaine was measured in Sprague-Dawley rats with behavioral-economic demand curve analysis after pretreatment with the OX1R antagonist SB-334867 (SB) or vehicle with and without light + tone cues. Demand for cocaine was higher when cocaine-associated cues were present, and SB only reduced cocaine demand in the presence of these cues. We then investigated whether cocaine demand was linked to the cued reinstatement of cocaine seeking, as both procedures are partially driven by cocaine-associated cues in an orexin-dependent manner. SB blocked cue-induced reinstatement behavior, and ba...Continue Reading

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Citations

Feb 14, 2016·Psychopharmacology·Irina N KrasnovaJean Lud Cadet
Jan 7, 2016·Current Psychiatry Reports·Shi-Bin LiLuis de Lecea
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Jun 3, 2021·International Journal of Molecular Sciences·Jeffrey L BarrEugen Brailoiu

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