Investigating the neuroprotective effect of citalopram in a MDMA-lesioned rat model using 4-[18F]-ADAM/micro-PET

Objectives The MDMA is a recreational drug that may induce serotonergic toxicity in the brain. The citalopram is an antidepressant that targets to the brain serotonin transporters(SERT). The aim of this study was to explore the neuroprotective effects of citalopram in the MDMA-induced serotonergic toxicity of rat brain using 4-[18F]-ADAM (targeting to serotonin transporter)/micro-PET.

Methods The serotonergic neurons of primary culture were stained with tryptophan hydroxylase immunofluorescence to investigate the effect of citalopram on the MDMA-lesioned serotonergic neurons. In the in vivo studies, the citalopram (10mg/kg, i.p.) and MDMA (10mg/kg, s.c.) were treated concomitantly in the male Sprague-Dawley rats twice a day for 4 successive days. The 4-[18F]-ADAM/micro-PET imaging were performed at fourteen day after the drugs treatment. The specific uptake ratios (SURs) were calculated via depicting the regions of interest (ROI) in various regions of rat brains in reference to the cerebellum (i.e., [ROI-cerebellum]/cerebellum). In addition, forced swimming tests were also performed for evaluating the status of depression-like behaviors.

Results In the in vitro studies, the citalopram treatment could prevent the MDMA-induced atrophy of the serotonergic neurites. The PET imaging data show that the SURs of 4-[18F]-ADAM in various brain regions of MDMA-treated rats were significantly lower than those of normal rats. Whereas the SURs of 4-[18F]-ADAM in various brain regions of co-treatment group were markedly higher than those of MDMA-treated group. In the behavior study, the immobility time of forced swimming test in the co-treatment group was reduced compared to that of MDMA-treated group.

Conclusions The citalopram may provide protection for the MDMA-induced SERT loss in rat brain and the 4-[18F]-ADAM/micro-PET may be a feasible method for monitoring the status of SERT in vivo.