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5‐HT 1B Autoreceptors limit the effects of selective serotonin re‐uptake inhibitors in mouse hippocampus and frontal cortex
Author(s) -
Malagié Isabelle,
Trillat AnneCécile,
Bourin Michel,
Jacquot Christian,
Hen René,
Gardier Alain M.
Publication year - 2001
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2001.00083.x
Subject(s) - serotonergic , serotonin , paroxetine , hippocampus , microdialysis , medicine , endocrinology , 5 ht receptor , neurotransmitter , chemistry , receptor antagonist , autoreceptor , pharmacology , antagonist , receptor , biology , central nervous system
We used knockout mice and receptor antagonist strategies to investigate the contribution of the serotonin (5‐hydroxytryptamine, 5‐HT) 1B receptor subtype in mediating the effects of selective serotonin re‐uptake inhibitors (SSRIs). Using in vivo intracerebral microdialysis in awake mice, we show that a single systemic administration of paroxetine (1 or 5 mg/kg, i.p.) increased extracellular serotonin levels [5‐HT] ext in the ventral hippocampus and frontal cortex of wild‐type and mutant mice. However, in the ventral hippocampus, paroxetine at the two doses studied induced a larger increase in [5‐HT] ext in knockout than in wild‐type mice. In the frontal cortex, the effect of paroxetine was larger in mutants than in wild‐type mice at the 1 mg/kg, but not at 5 mg/kg. In addition, either the absence of the 5‐HT 1B receptor or its blockade with the mixed 5‐HT 1B/1D receptor antagonist, GR 127935, potentiated the effect of a single administration of paroxetine on extracellular 5‐HT levels more in the ventral hippocampus than in the frontal cortex. These data suggest that 5‐HT 1B autoreceptors limit the effects of SSRIs on dialysate 5‐HT levels at serotonergic nerve terminals.