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Abstract

Orexin‑producing neurons project to reward‑related regions and have been implicated in several drug‑associated behaviors, but their role in ethanol‑conditioned learning is unclear. This study examined whether blocking orexin 1 receptors (OX1R) with SB‑334867 affects the acquisition or expression of ethanol‑induced conditioned place preference (CPP) in DBA/2J mice. SB‑334867 did not alter baseline locomotion or the development of ethanol CPP, though it reduced ethanol‑induced locomotor stimulation at high doses and modestly increased blood ethanol levels. OX1R antagonism disrupted expression of a weak CPP but not a strong one. Overall, OX1R blockade did not meaningfully influence ethanol CPP, suggesting other neurotransmitter systems can compensate for reduced orexin signaling.

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