Effect of different challenge doses after repeated citalopram treatment on extracellular serotonin level in the medial prefrontal cortex: in vivo microdialysis study

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.