Neuroscience 2003 Abstract
| Presentation Number: | 460.7 |
|---|---|
| Abstract Title: | Functional inactivation of serotonin 5-HT2C receptors as a mechanism to enhance acute neurochemical and behavioral effects of SSRIs. |
| Authors: |
Murphy, O. P.*1
; Giorgetti, M.1
; Tecott, L. H.1
1Dept. of Psychiatry, UC San Francisco, San Francisco, CA |
| Primary Theme and Topics |
Synaptic Transmission and Excitability - Neurotransmitters -- Serotonin |
| Session: |
460. Serotonin Behavior & Pharmacology Poster |
| Presentation Time: | Monday, November 10, 2003 3:00 PM-4:00 PM |
| Location: | Morial Convention Center - Hall F-I, Board # B69 |
| Keywords: |
We have recently observed that effects of acute fluoxetine (FLX) administration on prefrontal cortical serotonin (5HT) extracellular levels are enhanced in 5-HT2C receptor knock out mice compared to wild type controls; and that antidepressant-like behavioral responses induced by FLX are also significantly higher in these mice (Giorgetti et al., SFN 2002). Moreover, using a pharmacological approach, it has been shown that selective antagonism of this 5-HT receptor subtype also potentiates effects of different SSRIs on prefrontal cortical and hippocampal 5-HT levels in freely moving rats (Cremers et al., 2002). In order to expand these findings, we have used a pharmacological approach that is known to induce functional down-regulation of 5-HT2C receptors. Briefly, C57BL/6 mice were treated with either saline (SAL-10 ml/kg ip) or the 5-HT2C/2A receptor agonist m-CPP (5 mg/kg ip) twice a day (9 AM and 6 PM) for 14 consecutive days (this protocol of m-CPP treatment has been previously shown to induce functional down-regulation of 5-HT2C receptors in brain areas that control mood and affect). On day 15, SAL and m-CPP chronically treated mice received either SAL administration or different doses of FLX (5-10-20 mg/kg ip), and the antidepressant response was measured using tail suspension test (TST- a behavioral paradigm that is supposed to measure antidepressant-like effects of SSRIs). We found that a dose of FLX (5mg/kg ip), that does not exert significant antidepressant-like responses in mice chronically treated with SAL, elicited a robust reduction in immobility time in animals that received repeated m-CPP treatment. However, antidepressant-like response to SAL administration in mice chronically treated with m-CPP was not different from control. These data along with our previous findings strongly suggest that functional inactivation of 5-HT2C receptors represents a potential new approach for boosting effects of SSRIs.
Sample Citation:
[Authors]. [Abstract Title]. Program No. XXX.XX. 2003 Neuroscience Meeting Planner. New Orleans, LA: Society for Neuroscience, 2003. Online.
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