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 cocaineprimed reinstatement, which was blocked by VTA infusions of the selective GABA B 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.

The Lateral Preoptic Area: A Novel Regulator of Reward Seeking and Neuronal Activity in the Ventral Tegmental Area

“…The role of GABA neurons of the VTA in reinstatement of drug seeking behaviors has not been extensively studied, but recent findings suggest that GABA neurons also play a role. Increasing GABA transmission in the VTA reduces dopamine levels in the nucleus accumbens and suppresses seeking behavior (Jin et al, 2018); it also attenuates the ability of cues to trigger reward seeking (Wakabayashi et al, 2019). Therefore, together, the decrease in activity of GABA neurons of the VTA and the increase in the activity of dopamine neurons could work to drive the reinstatement of seeking we observed.…”

“…The LPO sends monosynaptic glutamatergic and GABAergic projections to the ventral tegmental area (VTA) (Phillipson, 1979;Geisler and Zahm, 2005;Watabe-Uchida et al, 2012;Ogawa et al, 2014;Beier et al, 2015;Kalló et al, 2015), which is a critical regulator of drug seeking and taking. Stimuli that increase the activity of dopamine neurons of the VTA increase cocaine seeking and those that increase GABA transmission in the VTA decrease seeking (Phillips et al, 2003;Marinelli et al, 2006;Wise, 2013;Jin et al, 2018). Furthermore, the LPO projects to brain regions that influence the activity of VTA neurons, including, but not limited to, the lateral habenula (Mok and Mogenson, 1972;Kowski et al, 2008;Yetnikoff et al, 2015;Barker et al, 2017), rostromedial tegmental nucleus (Jhou et al, 2009;Yetnikoff et al, 2015), and dorsal raphe (Peyron et al, 1998;Ogawa et al, 2014).…”

Applications of Acupuncture Therapy in Modulating Plasticity of Central Nervous System

“…The effects of acupuncture on the γ‐Aminobutyric acid (GABA) inhibitory system is also explored. Jin et al reported that acupuncture at Shenmen (HT7) attenuated cocaine‐primed reinstatement and neuronal activation in the nucleus accumbens induced by acute cocaine administration. Interestingly, injection of GABA B receptor antagonist blocked the effects of HT7 acupuncture .…”

“…Jin et al reported that acupuncture at Shenmen (HT7) attenuated cocaine‐primed reinstatement and neuronal activation in the nucleus accumbens induced by acute cocaine administration. Interestingly, injection of GABA B receptor antagonist blocked the effects of HT7 acupuncture . The GABAergic system was also shown to induce acupuncture's neuroprotection in MCAO rats.…”

Acupuncture on the Stress‐Related Drug Relapse to Seeking

“…Indeed, activation of VTA GABA neurons by optogenetic stimulation inhibits dopamine neuronal activity in the VTA and in turn decreases dopamine release in the NAc [ 105 ]. Interestingly, the recent study showed that acupuncture at Shenmen (HT7) points attenuated cocaine-primed reinstatement, cocaine inhibition of GABA neuron activity in the VTA, and acute cocaine-induced dopamine release in the NAc, which were reversed by local infusion of the selective GABAB receptor antagonist 2-hydroxysaclofen [ 106 ]. These results suggest that acupuncture may reduce relapse to cocaine-seeking behavior by enhancement of GABAergic inhibition in the VTA.…”