MDMA treatment 6 months earlier attenuates the effects of CP-94,253, a 5-HT 1B receptor agonist, on motor control but not sleep inhibition

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The possible long-term effects of the recreational drug “ecstasy” ( 3,4-methylenedioxymethamphetamine, MDMA) on the function of 5-hydroxytryptamine-1B (5-HT 1B) receptor in sleep and motor control were investigated using a selective 5-HT 1B receptor agonist, 5-propoxy-3-(1,2,3,6-tetrahydro-4-pyrinzidyl)-1 H-pyrrolo [3,2- b] pyridine hydrochloride (CP-94,253; 5 mg/kg). CP-94,253 or vehicle was administered to freely moving rats pre-treated with MDMA (15 mg/kg) or vehicle 6 months earlier, and polygraphic recording for 24 h and motor activity measurements were performed. Active wake (AW), passive wake (PW), light slow wave sleep (SWS-1), deep slow wave sleep (SWS-2), paradoxical sleep (PS), and diurnal rhythm were analyzed for the whole period. In additional, the EEG power spectrum was calculated for the second hour after the acute treatment for AW, PW, SWS-1, and SWS-2. 5-HT transporter (5-HTT) immunohistochemistry was measured in brain areas related to sleep and motor control 6 months after MDMA treatment. CP-94,253 increased AW and PW, decreased SWS-2 and PS, and altered parameters of diurnal rhythm in control animals. CP-94,253 decreased the EEG power spectra at higher frequencies. The effects of CP-94,253 on AW and diurnal rhythm were reduced or eliminated in MDMA-treated animals. MDMA treatment decreased 5-HTT fibre density in posterior hypothalamus, tuberomammillary nucleus, caudate putamen and ventrolateral striatum. These data suggest that long-term changes in 5-HT 1B receptor function occur after serotonergic damage caused by a single dose of MDMA.