Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB₁ receptors

Abstract

Fu L-W, Longhurst JC. Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB1 receptors. J Appl Physiol 106: 1800 -1809, 2009. First published April 9, 2009 doi:10.1152/japplphysiol.91648.2008.-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. ␥-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 (CB1) 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 CB1 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 CB1 receptors with AM251, a selective CB1 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 Ϯ 373 vs. 33.8 Ϯ 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 CB1 receptor mechanism. somatic afferents; sympathoexcitatory reflex; cannabinoid type 1 receptor; microdialysis ELECTROACUPUNCTURE (EA), a potent alternative to manual acupuncture, has been suggested to be effective in treating certain cardiovascular diseases including hypertension, arrhythmias, and angina pectoris (5, 6, 41). Clinically, EA at the NeiguanJianshi (P5-6) acupoints has been used to treat cardiovascular diseases in Eastern and, more recently, Western countries (5, 21, 41). We and others have demonstrated that EA at P5-6 acupoints overlying the median nerve on the wrist modulate blood pressure elevation evoked by gastric distension (GD) in rats (27) or by gallbladder stimulation in cats (50) through a long-loop neural pathway, extending from the arcuate...

Medullary GABAergic mechanisms contribute to electroacupuncture modulation of cardiovascular depressor responses during gastric distention in rats

“…(8,19,42). In this regard, we have shown that repeated gastric distention induces consistent increases in arterial pressure in normoxic normocapnic rats and that EA modulates these pressor responses (8,12,19,42,48,49). Fewer studies have reported that gastric distention also can reflexly decrease blood pressure (29,39).…”

“…Excitatory and inhibitory neuropeptides in these cardiovascular regions contribute to the inhibition of visceral reflex evoked rVLM neuronal activity during EA (20,27,42,44). In addition to serotonin, nociceptin, endocannabinoids, and opioids (8,21,27,42), GABA, through stimulation of GABA A receptors in the vlPAG and rVLM, participates in the modulating actions of EA (12,42,44).We have demonstrated that EA at P5-P6 acupoints reduces excitatory cardiovascular responses and lowers sustained hypertension by decreasing sympathetic outflow (17,40,42). Although others have suggested that EA at P5-P6 acupoints is able to raise arterial blood pressure when it is low (36, 47), the central neural processing mechanisms underlying this action of EA have not been elucidated.…”

“…Excitatory and inhibitory neuropeptides in these cardiovascular regions contribute to the inhibition of visceral reflex evoked rVLM neuronal activity during EA (20,27,42,44). In addition to serotonin, nociceptin, endocannabinoids, and opioids (8,21,27,42), GABA, through stimulation of GABA A receptors in the vlPAG and rVLM, participates in the modulating actions of EA (12,42,44).…”

GABA in nucleus tractus solitarius participates in electroacupuncture modulation of cardiopulmonary bradycardia reflex

“…Nuclei in the hypothalamus, midbrain, and medulla process this somatic input during EA to modulate sympathoexcitatory reflex responses (26,28,43). Several neurotransmitter systems, including opioids and ␥-aminobutyric acid (GABA), participate in the inhibitory influence of acupuncture on excitatory cardiovascular responses (13,17,43,46). The activity of presympathetic neurons in the rostral ventrolateral medulla (rVLM) and nucleus raphé pallidus (NRP) are modulated by EA applied to P5-6 acupoints (27,28).…”

The Effect of Cannabis sativa Hydroalcoholic Extract on Sperm Parameters and Testis Histology in Rats

“…This is indicative of the role of the major components of Cannabis sativa (i.e. cannabinoids) in appetite and weight regulation (Fu & Longhurst, 2009). Since, in this study, Cannabis sativa extract could decrease the quality of sperm parameters including sperm count and motility, the negative effects of Cannabis sativa on sperm parameters and fertility should be taken into account.…”