5-HT1B Autoreceptors limit the effects of selective serotonin re-uptake inhibitorsin mouse hippocampus and frontal cortex.
Journal Title: Journal of Neurochemistry - Year 2001, Vol 76, Issue 3
Abstract
We used knockout mice and receptor antagonist strategies to investigatethe contribution of the serotonin (5-hydroxytryptamine, 5-HT) 1B receptor subtype in mediating the effectsof selective serotonin re-uptake inhibitors (SSRIs). Using in vivo intracerebral microdialysis in awakemice, we show that a single systemic administration of paroxetine (1 or 5 mg/kg, i.p.) increased extracellularserotonin 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 largerin mutants than in wild-type mice at the 1 mg/kg, but not at 5 mg/kg. In addition, either the absenceof the 5-HT1B receptor or its blockade with the mixed 5-HT1B/1D receptor antagonist, GR 127935, potentiatedthe effect of a single administration of paroxetine on extracellular 5-HT levels more in the ventralhippocampus than in the frontal cortex. These data suggest that 5-HT1B autoreceptors limit the effectsof SSRIs on dialysate 5-HT levels at serotonergic nerve terminals.
Authors and Affiliations
, A C Trillat, M Bourin, C Jacquot, R Hen, A M Gardier
Keywords
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5-HT1B Autoreceptors limit the effects of selective serotonin re-uptake inhibitorsin mouse hippocampus and frontal cortex.
We used knockout mice and receptor antagonist strategies to investigatethe contribution of the serotonin (5-hydroxytryptamine, 5-HT) 1B receptor subtype in mediating the effectsof selective serotonin re-uptake inhibitors...