Electroacupuncture suppresses morphine reward-seeking behavior: Lateral hypothalamic orexin neurons implicated

The orexin system specifically located in the lateral hypothalamus (LH) has been shown to play a unique role in reward seeking, drug relapse, and addiction. In this study, we investigated the effects of electroacupuncture (EA) on morphine conditioned place preference (CPP), reinstatement of extinguished CPP, and the expression of orexin in the LH. A two-chamber CPP model was used to measure the rewarding properties of morphine. 2Hz EA at points BL23 and ST36 was carried out for 30min daily before morphine injection on three conditioning days. The extinguished CPP was reinstated by systemic morphine injection. Immunohistochemistry was used to detect orexin-positive nuclei in the LH. The findings indicated that the expression of morphine-induced CPP can be effectively suppressed by EA. EA suppressed orexin-positive nuclei in the LH compared with morphine-conditioned rats. A combination of EA and orexin A antagonist (10mg/kg, i.p.) produced a significant decrease in the morphine reinstatement scores. The results indicate the possibility that orexin may be involved in the acupuncture effect on drug-seeking behavior and thereby has an important role in modulating acupuncture. The synergetic use of a protocol consisting of EA and low-dose orexin A antagonist may provide a novel treatment strategy for drug reward seeking and relapse.