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Changes in extrasynaptic GABAA receptors in the periaqueductal gray with morphine tolerance (659.7)
Author(s) -
Tonsfeldt Karen,
Li Minghua,
Suchland Katherine,
Ingram Susan
Publication year - 2014
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.28.1_supplement.659.7
Subject(s) - gabaa receptor , bicuculline , chemistry , periaqueductal gray , gaba receptor antagonist , inhibitory postsynaptic potential , pharmacology , agonist , receptor , postsynaptic potential , endocrinology , medicine , opioid , μ opioid receptor , tonic (physiology) , central nervous system , biology , biochemistry , midbrain
Mu‐opioid receptors (MOPrs) reduce GABA‐mediated inhibition of periaqueductal gray (PAG) output neurons to activate the descending pain modulatory system and induce antinociception. The role of extrasynaptic GABAA receptors and tonic inhibition of PAG neurons in antinociception has not been explored. Rats were treated twice a day with saline or morphine (5 mg/kg, sc.) for 3 days. Superfusion of the GABAA antagonist, bicuculline (10 µM), inhibited miniature inhibitory postsynaptic currents and blocked a resting current, indicating the presence of both synaptic and extrasynaptic GABAA‐mediated currents in the PAG. Bicuculline reduced the holding current in saline rats 18 ± 4 pA (n = 10), with less effect in morphine rats (2 ± 1 pA, n = 6, p < 0.05). The bicuculline currents reversed at the expected chloride potential in chloride (‐24 ± 3 mV) and gluconate (‐84 ± 2 mV) intracellular solutions, suggesting the current is mediated by GABAA receptors. Tonic currents are often mediated by extrasynaptic GABAA receptors containing the delta‐subunit. THIP (10 µM), a GABAA delta subunit receptor agonist, induced currents in naïve and morphine treated slices (84 ± 22 pA, n= 8; 77 ± 24 pA, n = 6). The THIP induced currents were reduced by prior administration of met‐enkephalin (10 µM) (30 ± 7 pA, n = 5) compared to control (74 ± 16 pA, n = 7 , p < 0.05). These results suggest GABAA delta receptors may be modulated by activation of MOPrs in the PAG. Grant Funding Source : DA027625