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MDMA ('Ecstasy') enhances 5-HT(1A) receptor density and 8-OH-DPAT- induced hypothermia: Blockade by drugs preventing 5-hydroxytryptamine depletion

Abstract:

One week after a single administration of 3,4- methylenedioxymethamphetamine (MDMA · HCl, 30 mg/kg i.p.), 5-HT(1A) receptor density was significantly increased by approximately 25-30% in the frontal cortex and hypothalamus of rats. The increased density correlated with the potentiation of the hypothermic response to the 5-HT(1A) receptor agonist 8- hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 1 mg/kg s.c.). Hypothalamic 5-HT7 receptors, which also bind 8-OH-DPAT, were not changed, however, by MDMA. Fluoxetine (5 mg/kg s.c.), ketanserin (5 mg/kg s.c.) or haloperidol (2 mg/kg i.p.), given 15 min prior to MDMA, prevented the depletion of 5- hydroxytryptamine (5-HT) induced by MDMA and also blocked the effects of this neurotoxin on 5-HT(1A) receptor density and on 8-OH-DPAT-induced hypothermia. The protection afforded by drugs against 5-HT loss did not correlate, however, with the antagonism of the acute hyperthermic effect of MDMA. The present results indicate that drugs able to prevent or to attenuate MDMA- induced 5-HT loss also prevent the changes in 5-HT(1A) receptor density as well as the enhanced hypothermic response to the 5-HT(1A) receptor agonist 8- OH-DPAT in MDMA-treated rats.