We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
S01-04 - 5-HT<sub>2C</sub> receptor activation inhibits stress-induced increase in 5-HT transmission: relevance to the effects of antidepressant drugs
- Authors
Mongeau, R.; Martin, C.; Chevarin, C.; Maldonaldo, R.; Hamon, M.; Robledo, P.; Lanfumey, L.
- Abstract
Objectives: 5-HT2C receptors are well known to be involved in anxiety, but their implication in stress-induced changes of 5-HT transmission remained to be investigated. We thus assess the behavioral and neurochemical effects of 5-HT2C receptor activation in naïve and stressed mice, and after chronic paroxetine known to exert anxiolytic effects in humans. Methods and results: The effects of the preferential 5-HT2C agonists m-chlorophenylpiperazine (mCPP) and RO60-0175, the selective 5-HT2C receptor antagonist SB242,084 and restraint-stress on anxiety-like behavior in mice were assessed using the social interaction test, while the neurochemical effects of these treatments on 5-HT turnover (5-HIAA/5-HT ratio) and extracellular 5-HT were determined using HPLC and microdialysis. Both mCPP and restraint-stress increased anxiety-like behavior in the social interaction test, and these effects were blocked by pretreatment with SB242,084. Restraint-stress increased 5-HT turnover in various brain areas, and this effect could be prevented by the 5-HT2C receptor agonist RO60-0175. Acute administration of SB242,084 potentiated the stress-induced increase in 5-HT turnover and blocked the inhibitory effect of RO60-0175. Microdialysis studies in frontal cortex revealed that RO60-0175 has an inhibitory effect on the stress-induced increase in extracellular 5-HT levels, but not on basal 5-HT levels. Chronic paroxetine prevented the anxiogenic effect of mCPP and prevented the inhibitory effect of RO60-0175 on restraint-stress-induced increase in 5-HT turnover. Conclusions: These data strongly suggest that 5-HT2C receptor activation mediates the anxiogenic effect of stress. In addition, the anxiolytic action of long term treatment with SSRIs might be causally related to a clear-cut 5-HT2C receptor desensitization.
- Subjects
ANTIDEPRESSANTS; SEROTONIN; PHYSIOLOGICAL stress; PAROXETINE; LABORATORY mice; BRAIN physiology; HIGH performance liquid chromatography; MICRODIALYSIS
- Publication
European Psychiatry, 2010, Vol 25, p124
- ISSN
0924-9338
- Publication type
Abstract
- DOI
10.1016/S0924-9338(10)70124-3