Acupuncture suppresses reinstatement of morphine-seeking behavior induced by a complex cue in rats

•Prevention of relapse is an important problem in the treatment of drug addiction.•Acupuncture at SI5 attenuated the reinstatement of morphine-seeking behavior.•Acupuncture at SI5 did not influence the food-taking and -seeking behavior.•Acupuncture's suppression was inhibited by GABA receptor antagonists.•Effect of acupuncture is mediated, at least in part, via GABA receptor system. Morphine causes physical and psychological dependence for individuals after repeated-use. Above all, our previous study showed that acupuncture attenuated reinstatement of morphine-seeking behavior induced by pharmacological cue. In this study, we investigated whether acupuncture could suppress the reinstatement of morphine-seeking behavior induced by the combination of environmental and pharmacological cues and the possible neuronal involvement. Male Sprague-Dawley rats were trained to self-administer morphine (1.0mg/kg) for 3 weeks. Following the withdrawal phase (7 days), the effects of acupuncture on reinstatement of morphine-seeking behavior were investigated. For the investigation of neuronal involvement, the GABAA receptor antagonist bicuculline and the GABAB receptor antagonist SCH 50911 were pre-treated. Morphine-seeking behavior induced by combination of re-exposure to the operant chamber and morphine injection was suppressed perfectly by acupuncture at SI5, but not at the control acupoint LI5 and this effect was blocked by pre-treatment with the GABA receptor antagonists. This study suggests that acupuncture at SI5 can be considered as a predominant therapy for the reinstatement of morphine-seeking behavior in humans.