Changes in extrasynaptic GABAA receptors in the periaqueductal gray with morphine tolerance (659.7)

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 rece...