期刊
PSYCHIATRY AND CLINICAL NEUROSCIENCES
卷 62, 期 5, 页码 568-574出版社
WILEY
DOI: 10.1111/j.1440-1819.2008.01851.x
关键词
citalopram; in vivo brain microdialysis; medial prefrontal cortex; serotonin; SSRI
资金
- Japanese Ministry of Education, Science and Culture [16659299, 19591333]
- Grants-in-Aid for Scientific Research [19591333, 16659299] Funding Source: KAKEN
Aims: In order to elucidate the relevance between the delayed onset of clinical efficacy of selective serotonin re-uptake inhibitors (SSRI) and extracellular 5-HT levels in the medial prefrontal cortex, the present study compared the ability of low-dose (3 mg/kg) and high-dose (30 mg/kg) citalopram to increase extracellular 5-HT levels in the medial prefrontal cortex following repeated citalopram treatment using in vivo microdialysis. Methods: An SSRI, citalopram, was given 10 mg/kg, s.c. twice daily for 6 days and once on the seventh day in rats. On the eighth day, rats received a single injection of citalopram (3 or 30 mg/kg s.c.), and extracellular 5-HT levels were assessed in the medial prefrontal cortex of rats using in vivo brain microdialysis. Results: There was no significant difference in basal extracellular 5-HT levels between the repeated citalopram group and the repeated saline group. The low-challenge dose of citalopram (3 mg/kg) produced significantly greater increases (170-200% at each time point) in the repeated citalopram group than in the repeated saline group (150%). The high-challenge dose of citalopram (30 mg/kg), however, increased extracellular 5-HT levels by 200-250% of basal levels in the repeated citalopram group, which was similar to the increases in the repeated saline group. Conclusions: Repeated SSRI treatment enhances the effect of low-dose SSRI on extracellular 5-HT levels but not that of high-dose SSRI.
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