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5‐HT 4 receptor‐mediated modulation of 5‐HT release in the rat hippocampus in vivo
Author(s) -
Ge Jian,
Barnes Nicholas M.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb15309.x
Subject(s) - 5 ht receptor , in vivo , hippocampus , neuroscience , chemistry , receptor , serotonin , pharmacology , biology , biochemistry , microbiology and biotechnology
1 In the present study, the ability of the 5‐hydroxytryptamine 4 receptor (5‐HT 4 receptor) to modulate the release of 5‐HT in the hippocampus of freely‐moving rats was investigated by the in vivo microdialysis technique. 2 The 5‐HT 4 receptor agonist, renzapride (1.0–100 μ m , administered via the microdialysis probe) increased extracellular hippocampal levels of 5‐HT in a concentration‐dependent manner (approximately 200% maximal increase). The ability of renzapride (100 μ m , administered via the microdialysis probe) to elevate extracellular levels of 5‐HT remained in the presence of the selective 5‐HT reuptake blocker, paroxetine (1.0 μ m , administered via the microdialysis probe). Furthermore, another 5‐HT 4 receptor agonist 5‐methoxytryptamine (5‐MeOT; 10 μ m , administered via the microdialysis probe, in the presence of the non‐5‐HT 4 5‐HT receptor antagonists pindolol (10 μ m ) and methysergide (10 μ m )) maximally elevated extracellular levels of 5‐HT by approximately 450% in the rat hippocampus. The elevation of extracellular 5‐HT levels induced by either renzapride (100 μ m ) or 5‐MeOT (10 μ m ) was completely prevented by combined administration of the selective 5‐HT 4 receptor antagonist, GR113808 (100 nM, administered via the microdialysis probe). GR113808 (100 nM, administered via the microdialysis probe) administered alone, however, reduced extracellular hippocampal 5‐HT levels by some 60%. 3 Systemic administration of the 5‐HT 1A receptor agonist, 8‐OH‐DPAT (0.1 mg kg −1 , s.c.) reduced extracellular levels of 5‐HT in the rat hippocampus by approximately 40%. Prior administration of 8‐OH‐DPAT (0.1 mg kg −1 , s.c.), with an associated reduction of extracellular hippocampal 5‐HT levels by approximately 40–50%, however, failed to prevent a subsequent elevation of extracellular levels of 5‐HT induced by renzapride (100 μ m , administered via the microdialysis probe). 4 Systemic administration of the 5‐HT 4 receptor agonist, renzapride (0.25 and 1.0 mg kg −1 , i.p.) increased extracellular levels of 5‐HT in the hippocampus in a dose‐dependent manner. The higher dose of renzapride increasing extracellular 5‐HT levels by some 200%. The selective 5‐HT4 receptor antagonist, GR125487D (1.0–100 μg kg −1 , i.p.) caused a dose‐dependent reduction in extracellular levels of 5‐HT in the hippocampus (maximally approximately 80% reduction). Prior administration of GR125487D (10 μg kg −1 , i.p.) prevented the elevation of extracellular levels of 5‐HT induced by renzapride (1.0 mg kg −1 , i.p.). 5 In conclusion, the present study provides evidence that activation of the 5‐HT 4 receptor facilitates 5‐HT release in the rat hippocampus in vivo .