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GABA‐mediated inhibitory effects of nitric oxide in the gracile nucleus on sensory neuropathies in Zucker Diabetic Fatty rats
Author(s) -
Rong Peijing,
Ma Shengxing
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.945.8
Subject(s) - picrotoxin , microdialysis , inhibitory postsynaptic potential , chemistry , nitric oxide , endocrinology , medicine , nociception , anesthesia , gabaa receptor , receptor , central nervous system
The purpose of this work is to determine the effects of nitric oxide (NO) and GABA transmission in the gracile nucleus (GN) on functional neuropathic changes in Zucker Diabetic Fatty (ZDF) rats. A microdialysis probe was implanted into the GN and an infusion fluid was pumped at 3.0 μ/min. 3‐Morpholinyl‐sydnoneimine hydrochloride (SIN‐1, 10 μM) was dissolved in artificial cerebrospinal fluid (ACSF) and infused into the GN in the presence or absence of picrotoxin (30 μM). Time‐response curves were determined by measurements of the mechanical threshold and withdrawal latencies to hot and cold stimuli during infusion for 20 minutes and at 20, 40, and 60 minutes after microinfusion of the compounds. The withdrawal latencies to mechanical, cold and hot stimuli were significantly increased following infusion of SIN‐1 but not altered by infusion of ACSF. The responses to SIN‐1 on withdrawal latencies to mechanical, cold and hot stimuli were consistently inhibited by picrotoxin in the dialysis fluid. These results demonstrate that the functional neuropathic changes in ZDF rats are improved by administration of NO donor in the GN and the responses are blocked by inhibition of GABA transmission. We conclude that GABA transmission mediates NO effects in the GN, which produces an inhibitory modulation of somatosensory/nociceptive susceptibility in Type II diabetes. Supported by ADA 7‐07‐RA‐100 and NIH RO1 AT 002478 to S. Ma.