Farzana Akter Koly, Christopher Dao / Psychology / Faculty Mentor: Linda Perrotti
Morphine strongly activates the brain’s reward circuitry and stimulates orexin neurons in the lateral hypothalamus (LH), which play a key role in reward processing. The orexin-1 receptor (OrxR1) is implicated in reward-seeking behaviors, but its role in morphine-associated reward, particularly sex differences, remains unclear. This study examined whether systemic administration of the OrxR1 antagonist SB334867 reduces morphine-induced conditioned place preference (CPP) in male and female rats. Twenty-three Long Evans rats underwent a seven-day CPP paradigm, receiving SB334867 (30 mg/kg, IP) or vehicle 30 minutes before morphine (10 mg/kg, SC) during conditioning. CPP expression was assessed, followed by brain extraction and immunohistochemistry to examine c-Fos and orexin co-expression. Results showed that females developed morphine CPP, which was attenuated by SB334867. Additionally, SB334867 reduced c-Fos expression in orexin-expressing LH neurons.These findings suggest that OrxR1 antagonism disrupts reward-related circuits, reducing morphine-induced CPP, particularly in females. This supports the potential of OrxR1 antagonists as therapeutic targets for opioid addiction. Support provided by National Institutes of Health, National Institute of Drug Abuse under award number R15DA055201 to LIP.
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