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Processing cardiovascular information in the vlPAG during electroacupuncture in rats: roles of endocannabinoids and GABA

Susan Samueli Center for Integrative Medicine, Department of Medicine, School of Medicine, University of California, Irvine, Irvine, California

Submitted 9 February 2009 ; accepted in final form 19 March 2009

A long-loop pathway, involving the hypothalamic arcuate nucleus (ARC), ventrolateral periaqueductal gray (vlPAG), and the rostral ventrolateral medulla (rVLM), is essential in electroacupuncture (EA) attenuation of sympathoexcitatory cardiovascular reflex responses. The ARC provides excitatory input to the vlPAG, which, in turn, inhibits neuronal activity in the rVLM. Although previous studies have shown that endocannabinoid CB₁ receptor activation modulates -aminobutyric acid (GABA)-ergic and glutamatergic neurotransmission in the dorsolateral PAG in stress-induced analgesia, an important role for endocannabinoids in the vlPAG has not yet been observed. We recently have shown (Fu LW, Longhurst JC. J Appl Physiol; doi:10.1152/japplphysiol.91648.2008) that EA reduces the local vlPAG concentration of GABA, but not glutamate, as measured with high-performance liquid chromatography from extracellular samples collected by microdialysis. We, therefore, hypothesized that, during EA, endocannabinoids, acting through CB₁ receptors, presynaptically inhibit GABA release to disinhibit the vlPAG and ultimately modulate excitatory reflex blood pressure responses. Rats were anesthetized, ventilated, and instrumented to measure heart rate and blood pressure. Gastric distention-induced blood pressure responses of 18 ± 5 mmHg were reduced to 6 ± 1 mmHg by 30 min of low-current, low-frequency EA applied bilaterally at pericardial P 5–6 acupoints overlying the median nerves. Like EA, microinjection of the fatty acid amide hydrolase inhibitor URB597 (0.1 nmol, 50 nl) into the vlPAG to increase endocannabinoids locally reduced the gastric distention cardiovascular reflex response from 21 ± 5 to 3 ± 4 mmHg. This inhibition was reversed by pretreatment with the GABA_A antagonist gabazine (27 mM, 50 nl), suggesting that endocannabinoids exert their action through a GABAergic receptor mechanism in the vlPAG. The EA-related inhibition from 18 ± 3 to 8 ± 2 mmHg was reversed to 14 ± 2 mmHg by microinjection of the CB₁ receptor antagonist AM251 (2 nmol, 50 nl) into the vlPAG. Pretreatment with gabazine eliminated reversal following CB₁-receptor blockade. Thus EA releases endocannabinoids and activates presynaptic CB₁ receptors to inhibit GABA release in the vlPAG. Reduction of GABA release disinhibits vlPAG cells, which, in turn, modulate the activity of rVLM neurons to attenuate the sympathoexcitatory reflex responses.

somatic afferents; splanchnic afferents; gastric distention; cannabinoid 1 receptor; -aminobutyric acid a receptor

This article has been cited by other articles:

				L.-W. Fu and J. C. Longhurst Electroacupuncture modulates vlPAG release of GABA through presynaptic cannabinoid CB1 receptors J Appl Physiol, June 1, 2009; 106(6): 1800 - 1809. [Abstract] [Full Text] [PDF]