Neuroscience Letters 529 (2012) 23–27 Contents lists available at SciVerse ScienceDirect Neuroscience Letters jou rn al h om epage: www.elsevier.com/locate/neulet Acupuncture at SI5 attenuates morphine seeking behavior after extinction Bong Hyo Lee a,∗ , Jeong Hun Ma a , Sunghyun In a , Hee Young Kim b , Seong Shoon Yoon b , Eun Young Jang b , Chae Ha Yang b a Department of Acupuncture, Moxibustion and Acupoint, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, South Korea b Department of Physiology, College of Oriental Medicine, Daegu Haany University, Daegu 706-828, South Korea h i g h l i g h t s ◮ Relapse to the drug is a serious problem in the treatment of addiction. ◮ Acupuncture at SI5 attenuated the reinstatement of morphine seeking behavior. ◮ Acupuncture’s suppression of relapse to the morphine is mediated, at least in part, via GABA pathway. a r t i c l e i n f o Article history: Received 28 May 2012 Received in revised form 31 August 2012 Accepted 10 September 2012 Keywords: Acupuncture Morphine Extinction Drug seeking Reinstatement GABA a b s t r a c t Our previous studies have shown that acupuncture attenuates morphine self-administration and sensi- tization behavior as well as withdrawal signs. The present study was designed to investigate the role of acupuncture in the reinstatement of morphine seeking. Male Sprague-Dawley rats weighing 270–300 g were subjected to intravenous catheterization after food training. The animals were trained to self-administer morphine (1.0 mg/kg, 3 weeks), followed by extinction (1 week). Extinction conditions were introduced by substituting saline for morphine. The rats were then tested for reinstatement of morphine self-administration by a priming injection of morphine (0.25 mg/kg). To see whether acupuncture can reduce morphine reinstatement, acupuncture was per- formed at SI5 or LI5 for 1 min immediately before a morphine injection. To further test the involvement of gamma aminobutyric acid (GABA) receptors in acupuncture effects, GABA receptor antagonists were injected before acupuncture. In the present results, acupuncture at SI5, but not at control acupoint LI5 attenuated the reinstatement of morphine seeking behavior, which was blocked by the GABA receptor antagonists. It suggests that acupuncture can reduce the reinstatement of morphine seeking, possibly due to the mediation of GABA receptor system. © 2012 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Most drugs of abuse exert reinforcing effects by increasing extracellular dopamine (DA) release in the mesolimbic system, which is related with drug-seeking behavior [2,3,24]. Morphine, the most commonly used opioid for pain relief [28], also increases DA release in the nucleus accumbens (NAc) via gamma aminobutyric acid (GABA)-mediated disinhibition of DA neurons in the ventral tegmental area (VTA) [14] and causes neuronal changes associated with drug seeking or reinstatement behaviors after repeated use [9,31]. ∗ Corresponding author at: Department of Acupuncture, Moxibustion and Acu- point, College of Oriental Medicine, Daegu Haany University, 165 Sang-Dong, Suseong-Gu, Daegu 706-828, South Korea. Tel.: +82 53 770 2252; fax: +82 53 768 6340. E-mail address: dlqhdgy@dhu.ac.kr (B.H. Lee). Relapse to drug addiction is one of major problems in absti- nent individuals after prolonged exposure, and prevention of these behaviors is particularly important for treatment. Acupuncture, a representative traditional therapy in the eastern Asia, including Korea and China, has been suggested as a useful treatment for drug addiction [1,4]. Recently, neurochemical and behavioral studies have been carried out to identify the effectiveness of acupunc- ture in substance abuse. For example, acupuncture normalized increases in behavior [19,20], gene expressions [16,20], and extra- cellular DA level in the brain [15] induced by morphine. Cumulative evidence linking morphine addiction and control of DA level by acupuncture led us to hypothesize that acupuncture may prevent the reinstatement of morphine seeking behavior. Oriental medicine teaches that acupuncture at SI5 calms down mind or emotions by clearing the heat of heart meridian [8,22]. It is supported by a previous observation showing an inhibitory effect on locomo- tor activity and c-Fos expression elicited by methamphetamine [6]. 0304-3940/$ – see front matter © 2012 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neulet.2012.09.020