| 15301922 |
Yamauchi M, Tatebayashi T, Nagase K, Kojima M, Imanishi T: Chronic treatment with fluvoxamine desensitizes 5-HT2C receptor-mediated hypolocomotion in rats. Pharmacol Biochem Behav. 2004 Aug;78(4):683-9.
The effectiveness of fluvoxamine, a selective serotonin re-uptake inhibitor (SSRI), in the treatment of anxiety disorders, such as obsessive-compulsive, panic and social anxiety disorders, has been confirmed in clinical studies. The hypersensitivity of 5-HT2C receptors has been reported in subjects with these disorders, and SSRIs have been suggested to have therapeutic effects in such cases through the desensitization of the 5-HT2C receptor function. In the present study, we investigated whether chronic administration of fluvoxamine desensitizes 5-HT2C receptors using a putative in vivo rat model of 5-HT2C receptor function. Acute treatment with fluvoxamine or another SSRI, paroxetine, reduced spontaneous locomotion, as observed with the administration of m-chlorophenylpiperazine (mCPP). This effect of fluvoxamine was reversed by treatment with a selective 5-HT2C receptor antagonist, SB 242084. On the other hand, chronic treatment with fluvoxamine or paroxetine inhibited mCPP-induced hypolocomotion, while they had no effects in control rats. In addition, chronic treatment with these drugs had no effects on the mCPP concentration in the rat brain. These results suggest that 5-HT2C receptors are desensitized by chronic treatment with fluvoxamine, as well as paroxetine. Thus, the clinical efficacy of fluvoxamine on anxiety disorders might involve the normalization of the 5-HT2C receptor function. |
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