Aims: 

Selective serotonin reuptake inhibitors (SSRIs) are extensively used for the treatment of depression and anxiety disorders. In addition, ecstasy (3, 4-methylenedioxymethamphetamine, MDMA) users frequently suffer from depression and are often treated by SSRIs. Effects of citalopram on vigilance states were studied after serotonergic damage by MDMA treatment.

Methods: 

Seven-week-old male Dark Agouti rats received an injection of MDMA (15mg/kg, i.p.) or vehicle. Three weeks later, citalopram (2.5mg/kg, i.p.) or vehicle was administered, and 24h polysomnographic recordings (EEG, EMG, motor activity) were performed. Active and passive wakefulness, light and deep slow wave sleep, rapid eye movement (REM) sleep and REM sleep latency were calculated by sleep stating. We labeled serotonergic fibers with 5-HT transporter (5-HTT) immunohistochemistry. The functional state of 5-HT_1A receptors was assessed by quantifying [³⁵S]GTP-U-S-binding in response to stimulation by 5-carboxamido-tryptamine (5-CT).

Results: 

5-HTT density decreased by 30-40% in several hippocampal and hypothalamic but not brainstem regions after MDMA treatment. 5-CT-evoked [³⁵S] GTP-U-S-binding was reduced in hippocampus CA1 area but not dorsal raphe nucleus. MDMA treatment reduced REM sleep latency and increased the amount of REM at the beginning of sleep. Citalopram-induced decrease in REM had a shorter duration in MDMA-treated animals compared to controls.

Conclusion: 

Our findings suggest that reduction of PS is a useful measure of inhibition of 5-HT reuptake. These effects of SSRIs are likely altered in ecstasy users. Supported by: 5^th FP, QLG3-CT-2002-00809 and 6^th FP, LSHM-CT-2004-503474 of the E.C., HRF Grant D-048502.