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Evidence that 5‐HT neurotransmission within the nucleus tractus solitarii (NTS) differentially modulates glutamate release via 5‐HT 3 and 5‐HT 1A receptors
Author(s) -
Hosford Patrick S,
Ramage Andrew G,
Mifflin Steve
Publication year - 2013
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.27.1_supplement.932.6
Subject(s) - neurotransmission , granisetron , chemistry , receptor , agonist , 5 ht receptor , serotonin , reuptake , glutamatergic , receptor antagonist , 5 ht3 receptor , glutamate receptor , pharmacology , medicine , endocrinology , antagonist , biology , biochemistry , antiemetic , vomiting
The effects of spontaneously released 5‐HT were investigated in NTS containing slices (300 μm). Recordings were made of glutamatergic mEPSCs (abolished by CNQX) from voltage clamped (−60 mv) NTS neurones in the presence of gabazine (25 μmol) and TTX (1 μmol). Low doses (300μM; n=5) of 5‐HT inhibited (frequency decreased by 53±12%), while high doses 10μM increased mEPSC frequency (1285±276%) and amplitude (21±5 %). In presence of the 5‐HT 3 antagonist granisetron (3μM) 5‐HT now only caused a decrease (31±11%) in frequency. The 5‐HT 3 receptor agonist PBG (1μM) increased mEPSC frequency by 497±112% and amplitude by 18±4%, which was also blocked by granisetron. Granisetron (1μM; n=6) alone decreased mEPSC frequency by 35±4% as did the SSRI citalopram (0.5μM, n=5; 54±5%) and the OCT3 inhibitor decynium 22 (1μM; n=4; 27±2). The effects of the reuptake inhibitors were blocked by WAY‐100635 (1μM). The data indicates that the spontaneous release of 5‐HT in the NTS only activates presynaptically located 5‐HT 3 and 5‐HT 1A receptors. However, the ability of 5‐HT uptake blockade to only increase 5‐HT 1A receptor activation suggests that the ability of spontaneously released 5‐HT to activate presynaptic 5‐HT 3 receptors is not subject to modulation by reuptake. This would be consistent with these 5‐HT 3 receptors being heteroreceptors. These data shows that endogenous 5‐HT has two distinct modulatory actions on glutamate release.