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- Title
Effect of different challenge doses after repeated citalopram treatment on extracellular serotonin level in the medial prefrontal cortex: In vivo microdialysis study.
- Authors
Muraki, Ihoko; Inoue, Takeshi; Hashimoto, Shinji; Izumi, Takeshi; Koyama, Tsukasa
- Abstract
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.
- Subjects
DRUG dosage; SEROTONIN; PREFRONTAL cortex; MICRODIALYSIS; NEUROTRANSMITTERS; MEDICAL research
- Publication
Psychiatry & Clinical Neurosciences, 2008, Vol 62, Issue 5, p568
- ISSN
1323-1316
- Publication type
Article
- DOI
10.1111/j.1440-1819.2008.01851.x