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Scearce-Levie K, Viswanathan SS, Hen R.
“Locomotor response to MDMA is attenuated in knockout mice lacking the 5-HT1B receptor”.
Psychopharmacology (Berl). 1999 Jan;141(2):154-61.
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Abstract
3,4-Methylenedioxymethamphetamine (MD-MA) is a psychoactive drug of abuse which is increasingly popular in human recreational drug use. In rats, the drug has been shown to stimulate locomotion while decreasing exploratory behavior. MDMA acts as an indirect agonist of serotonin (5-HT) receptors by induc-ing 5-HT release by a 5-HT reuptake transporter-dependent mechanism, although it is not known which 5-HT receptors are important for the behavioral e¤ects of the drug. In order to examine the role of speciŽc 5- HT receptors, we assessed the behavioral e¤ects of MDMA on knockout mice lacking the 5-HT1B recep-tor. Knockout animals show a reduced locomotor response to MDMA, although delayed locomotor stim-ulation is present in these animals. This Žnding indi-cates that the locomotor e¤ects of MDMA are dependent upon the 5-HT1B receptor, at least in part. In contrast, MDMA eliminates exploratory behavior in both normal and knockout mice, suggesting that the exploratory suppression induced by MDMA occurs through mechanisms other than activation of the 5- HT1B receptor. To conŽrm these Žndings, we tested the e¤ects of MDMA on the locomotor and exploratory behavior of wild-type mice pretreated with GR 127935, a 5-HT1B/ 1D receptor antagonist. These mice had an attenuated locomotor response to MDMA, but still exhibited the drug-induced suppression of exploration.
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