title: Acupuncture reduces relapse to cocaine-seeking behavior via activation of GABA neurons in the ventral tegmental area.
abstract: There is growing public interest in alternative approaches to addiction treatment and scientific interest in elucidating the neurobiological underpinnings of acupuncture. Our previous studies showed that acupuncture at a specific Shenmen (HT7) points reduced dopamine (DA) release in the nucleus accumbens (NAc) induced by drugs of abuse. The present study was carried out to evaluate the effects of HT7 acupuncture on γ-aminobutyric acid (GABA) neuronal activity in the ventral tegmental area (VTA) and the reinstatement of cocaine-seeking behavior. Using microdialysis and in vivo single-unit electrophysiology, we evaluated the effects of HT7 acupuncture on VTA GABA and NAc DA release and VTA GABA neuronal activity in rats. Using a within-session reinstatement paradigm in rats self-administering cocaine, we evaluated the effects of HT7 stimulation on cocaine-primed reinstatement. Acupuncture at HT7 significantly reduced cocaine suppression of GABA release and GABA neuron firing rates in the VTA. HT7 acupuncture attenuated cocaine-primed reinstatement, which was blocked by VTA infusions of the selective GABABreceptor antagonist 2-hydroxysaclofen. HT7 stimulation significantly decreased acute cocaine-induced DA release in the NAc, which was also blocked by 2-hydroxysaclofen. HT7 acupuncture also attenuated cocaine-induced sensitization of extracellular DA levels in the NAc. Moreover, HT7 acupuncture reduced both locomotor activity and neuronal activation in the NAc induced by acute cocaine in a needle-penetration depth-dependent fashion. These results suggest that acupuncture may suppress cocaine-induced DA release in the NAc and cocaine-seeking behavior through activation of VTA GABA neurons. Acupuncture may be an effective therapy to reduce cocaine relapse by enhancing GABAergic inhibition in the VTA.
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Wyju
authors.initials: W
authors.lastname: Jin
authors.affiliation: Department of Physiology, School of Medicine, Wonkwang University, Iksan, South Korea.
authors.forename: Min Sun
authors.initials: MS
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.|Convergence Research Center, College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Eun Young
authors.initials: EY
authors.lastname: Jang
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Jun Yeon
authors.initials: JY
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Jin Gyeom
authors.initials: JG
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Hong Yu
authors.initials: HY
authors.lastname: Kim
authors.affiliation: Research Center of Safety Pharmacology, Korea Institute of Toxicity, Daejeon, South Korea.
authors.forename: Seong Shoon
authors.initials: SS
authors.lastname: Yoon
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Bong Hyo
authors.initials: BH
authors.lastname: Lee
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Suchan
authors.initials: S
authors.lastname: Chang
authors.affiliation: Department of Meridian & Acupoint, College of Korean Medicine, Wonkwang University, Iksan, South Korea.
authors.forename: Jae Hyo
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
authors.forename: Kwang H
authors.initials: KH
authors.lastname: Choi
authors.affiliation: Department of Physiology, School of Medicine, Wonkwang University, Iksan, South Korea.
authors.forename: Ho
authors.initials: H
authors.lastname: Koo
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.|Convergence Research Center, College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Young Seob
authors.initials: YS
authors.lastname: Gwak
authors.affiliation: Department of Psychology and Center for Neuroscience, Brigham Young University, Provo, UT, USA.
authors.forename: Scott C
authors.initials: SC
authors.lastname: Steffensen
authors.affiliation: Acupuncture, Moxibustion & Meridian Research Center, Division of Standard Research, Korea Institute of Oriental Medicine, Daejeon, South Korea.
authors.forename: Yeon-Hee
authors.initials: YH
authors.lastname: Ryu
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Hee Young
authors.initials: HY
authors.lastname: Kim
authors.affiliation: College of Korean Medicine, Daegu Haany University, Daegu, South Korea.|Convergence Research Center, College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
authors.forename: Chae Ha
authors.identifier: 0000-0002-4551-1600
authors.initials: CH
authors.lastname: Yang
mesh_terms: D026881:Acupuncture; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001522:Behavior, Animal; D003042:Cocaine / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D058999:Drug-Seeking Behavior; D055724:Electrophysiological Phenomena; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000378:metabolism; D008124:Locomotion; D017551:Microdialysis; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017557:Ventral Tegmental Area / Q000166:cytology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018765:Dopamine Uptake Inhibitors; D058788:GABA-B Receptor Antagonists; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D003042:Cocaine; D004298:Dopamine; C057491:2-hydroxysaclofen
keywords: Acupuncture; GABA; cocaine-seeking behavior; dopamine; ventral tegmental area