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 baseline demand predicted SB efficacy with the largest effect in high-demand animals, i.e. animals with the greatest cue-dependent behavior. We conclude that OX1R signaling increases the reinforcing efficacy of cocaine-associated cues but not that of cocaine alone. This supports our view that orexin plays a prominent role in the ability of conditioned cues to activate motivational responses.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.