Electroacupuncture modulates vIPAG release of GABA through presynaptic cannabinoid CB1 receptors

Department of Medicine, University of California, Irvine, CA 92697, USA.
Journal of Applied Physiology (Impact Factor: 3.06). 05/2009; 106(6):1800-9. DOI: 10.1152/japplphysiol.91648.2008
Source: PubMed


Previous studies have demonstrated that electroacupuncture (EA) attenuates sympathoexcitatory reflex responses by activating a long-loop pathway involving the hypothalamic arcuate nucleus (ARC), midbrain ventrolateral periaqueductal gray (vlPAG), and rostral ventrolateral medulla (rVLM). Neurons in the ARC provide excitatory input to the vlPAG, whereas the vlPAG inhibits neuronal activity in the rVLM. gamma-Aminobutyric acid (GABA) and glutamate (Glu) have been identified in the vlPAG. Endocannabinoids (ECs), acting as atypical neurotransmitters, inhibit the release of both neurotransmitters in the hypothalamus and midbrain through a presynaptic cannabinoid type 1 (CB(1)) receptor mechanism. The EC system has been observed in the dorsal but not in the vlPAG. Since it is uncertain whether ECs influence GABA and Glu in the vlPAG, the present study tested the hypothesis that EA modulates the release of these neurotransmitters in the vlPAG through a presynaptic CB(1) receptor mechanism. We measured the release of GABA and Glu simultaneously by using HPLC to assess samples collected with microdialysis probes inserted unilaterally into the vlPAG of intact anesthetized rats. Twenty-eight min of EA (2 Hz, 2-4 mA, 0.5 ms) at the P5-6 acupoints reduced the release of GABA by 39% during EA and by 44% 15 min after EA. Thirty-five minutes after EA, GABA concentrations returned to pre-EA levels. In contrast, sham EA did not change the vlPAG GABA concentration. Blockade of CB(1) receptors with AM251, a selective CB(1) receptor antagonist, reversed the EA-modulated changes in GABA concentration, whereas microinjection of vehicle into the vlPAG did not alter EA-modulated GABA changes. In addition, we observed no changes in the vlPAG Glu concentrations during EA, although the baseline concentration of Glu was much higher than that of GABA (3,541 +/- 373 vs. 33.8 +/- 8.7 nM, Glu vs. GABA). These results suggest that EA modulates the sympathoexcitatory reflex responses by decreasing the release of GABA, but not Glu, in the vlPAG, most likely through a presynaptic CB(1) receptor mechanism.

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    • "These include the arcuate and paraventricular nuclei in the hypothalamus (Li, Tjen-A-Looi, Guo, & Longhurst, 2010; Li, Tjen-A-Looi, & Longhurst, 2006; Tjen-A-Looi, Guo, & Longhurst, 2013), ventrolateral periaqueductal gray (vlPAG) in the midbrain (Li et al., 2009; Li, Tjen-A-Looi, Guo, et al., 2010), nucleus tractus solitarii (Tjen-A-Looi et al., 2012), rVLM (Moazzami, Tjen-A-Looi, Guo, & Longhurst, 2010; Tjen-A-Looi, Li, & Longhurst, 2003; Tjen-A- Looi et al., 2004), cVLM (Tjen-A-Looi et al., 2013), medullary raphe, particularly the raphe pallidus (Li, Tjen-A-Looi, & Longhurst, 2010b; Moazzami et al., 2010), and nucleus ambiguus (Guo, Li, & Longhurst, 2012; Tjen-A-Looi et al., 2012) in the medulla as well as the dorsal horn and intermediolateral columns of the spinal cord (Zhou, Mahajan, & Longhurst, 2009). Evoked somatic input is largely excitatory in these regions and relies most commonly on glutamate (Zhou, Fu, Guo, & Longhurst, 2007; Zhou, Fu, Tjen-A-Looi, Guo, & Longhurst, 2006), other excitatory neurotransmitters like acetylcholine (Li, Tjen-A-Looi, Guo, et al., 2010), or presynaptic disinhibition of inhibitory neurotransmitters (endocannabinoids acting to reduce release of g-aminobutyric acid or GABA) (Fu & Longhurst, 2009; Tjen-A-Looi et al., 2009). Acupuncture activates neurons in these regions, through a network of projections extending from the hypothalamus to more caudal regions like the vlPAG and rVLM and through inhibitory neurotransmitter mechanisms, including opioids (Li et al., 2009; Li, Tjen-A-Looi, & Longhurst, 2001; Tjen-A-Looi et al., 2003; Tjen-A-Looi, Li, & Longhurst, 2007), GABA (Fu & Longhurst, 2009; Tjen-A-Looi et al., 2007, 2009), nociceptin (Crisostomo et al., 2005; Tjen-A-Looi et al., 2007), or serotonin (Guo, Moazzami, Tjen-A- Looi, & Longhurst, 2008; Moazzami et al., 2010 "
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    • "And Fusumada et al. [126] proved that by inserting EA at " Zusanli " (ST36), EA could induce analgesic effect along with the increasing expression of GABA in PAG. Also, Fu and Longhurst [127] and Tjen-A-Looi et al. [128] studies reported that EA decreases the release of GABA in ventrolateral PAG, by modulating the sympathoexcitatory reflex responses through endocannabinoids. "
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    Evidence-based Complementary and Alternative Medicine 07/2013; 2013(3699):436913. DOI:10.1155/2013/436913 · 1.88 Impact Factor
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    • "In addition, reduction of GABA release disinhibits vlPAG cells, which, in turn, modulates the activity of rVLM neurons to attenuate the sympathoexcitatory reflex responses [46]. EA modulates the sympathoexcitatory reflex responses by decreasing the release of GABA in the vlPAG [43], most likely through a presynaptic CB1 receptor mechanism [72]. Studies conducted so far on amino acids suggest that glutamate and GABA are involved in the mechanism of acupuncture for autonomic alteration. "
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