College of Korean Medicine, Daegu Haany University, Daegu, South Korea.
Department of Physiology, School of Medicine, Wonkwang University, Iksan, South Korea.
Addict Biol. 2018 Jan;23(1):165-181. doi: 10.1111/adb.12499. Epub 2017 Mar 7.
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 GABA receptor 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.
人们对替代成瘾治疗方法的兴趣日益浓厚,科学界也对阐明针刺的神经生物学基础产生了浓厚兴趣。我们之前的研究表明,针刺特定的神门(HT7)穴位可减少药物滥用引起的伏隔核(NAc)中多巴胺(DA)的释放。本研究旨在评估 HT7 针刺对腹侧被盖区(VTA)中γ-氨基丁酸(GABA)神经元活动和可卡因觅药行为复吸的影响。使用微透析和体内单细胞电生理学,我们评估了 HT7 针刺对大鼠 VTA GABA 和 NAc DA 释放以及 VTA GABA 神经元活性的影响。在大鼠可卡因自我给药的单次疗程复吸范式中,我们评估了 HT7 刺激对可卡因引发复吸的影响。HT7 针刺可显著降低可卡因对 VTA GABA 释放和 GABA 神经元放电率的抑制作用。HT7 针刺可减弱可卡因引发的复吸,而 VTA 内注射选择性 GABA 受体拮抗剂 2-羟基苯甲酰芬可阻断这一作用。HT7 刺激可显著降低急性可卡因引起的 NAc 中 DA 的释放,而 2-羟基苯甲酰芬也可阻断这一作用。HT7 针刺还可减弱急性可卡因引起的 NAc 中细胞外 DA 水平的敏化作用。此外,HT7 针刺以针穿透深度依赖的方式降低了急性可卡因引起的 NAc 中运动活动和神经元激活。这些结果表明,针刺可能通过激活 VTA GABA 神经元来抑制 NAc 中可卡因诱导的 DA 释放和可卡因觅药行为。通过增强 VTA 中的 GABA 抑制作用,针刺可能成为减少可卡因复吸的有效治疗方法。