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• W2017356426 abstract "Augmentation of serotonergic neurotransmission at the level of the dorsal spinal cord is proposed to contribute to the analgesic activity of selective serotonin (5-HT) reuptake inhibitors (SSRIs). In this study we have utilised microdialysis perfusion to determine the effect of two structurally unrelated SSRIs on depolarisation-induced aspartate and glutamate release in the dorsal spinal cord of the anaesthetised rat. Perfusion with artificial extracellular fluid containing 45 mM potassium produced a significant increase in aspartate and glutamate efflux. Sensitivity, at least in part, to antagonism of calcium entry by high extracellular Mg2+ indicated a neuronal origin for a proportion of stimulated release. Reverse dialysis of paroxetine (1–30 μM) reduced the increase in glutamate in a concentration dependent manner, with a significant reduction evident following inclusion in the perfusate of 30 μM. Administration of an equi-potent dose of citalopram (300 μM) also reduced depolarisation induced glutamate release. Aspartate levels tended to decrease in the presence of paroxetine and citalopram, but this trend did not reach significance. Co-perfusion of paroxetine (30 μM) with the selective 5-HT1A receptor antagonist WAY 100635 (100 μM) did not prevent the reduction in depolarisation induced glutamate efflux. These results demonstrate that local administration of SSRIs has an inhibitory influence on evoked release of glutamate in the dorsal horn. This could indicate regulation of excitatory neurotransmission mediated through augmented serotonergic neurotransmission and activation of a serotonergic receptor other than the 1A subtype. Alternatively, direct inhibition with voltage dependent calcium channels, potentially a property intrinsic to molecules with high selectivity for the 5-HT transporter, may underlie this effect." @default.
• W2017356426 created "2016-06-24" @default.
• W2017356426 creator A5016647349 @default.
• W2017356426 creator A5035714899 @default.
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• W2017356426 date "2006-02-01" @default.
• W2017356426 modified "2023-10-07" @default.
• W2017356426 title "Selective serotonin re-uptake inhibition attenuates evoked glutamate release in the dorsal horn of the anaesthetised rat in vivo" @default.
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• W2017356426 doi "https://doi.org/10.1016/j.phrs.2005.10.003" @default.
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