Related Experiment Videos
Locomotor response to MDMA is attenuated in knockout mice lacking the 5-HT1B receptor
K Scearce-Levie1, S S Viswanathan, R Hen
1Center for Neurobiology and Behavior, Columbia Unversity, New York, NY 10032, USA.
Abstract:
3,4-Methylenedioxymethamphetamine (MDMA) 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 inducing 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 effects of the drug. In order to examine the role of specific 5-HT receptors, we assessed the behavioral effects of MDMA on knockout mice lacking the 5-HT1B receptor. Knockout animals show a reduced locomotor response to MDMA, although delayed locomotor stimulation is present in these animals. This finding indicates that the locomotor effects 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 confirm these findings, we tested the effects 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.
Insights
The 5-HT1B receptor plays a partial role in the locomotor stimulant effects of 3,4-Methylenedioxymethamphetamine (MDMA). However, MDMA
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- 3,4-Methylenedioxymethamphetamine (MDMA) is a popular recreational psychoactive drug.
- MDMA indirectly agonizes serotonin (5-HT) receptors by increasing 5-HT release.
- The specific 5-HT receptors mediating MDMA's behavioral effects are not fully understood.
Purpose of the Study:
- To investigate the role of the 5-HT1B receptor in mediating the behavioral effects of MDMA.
- To determine if 5-HT1B receptor activation is necessary for MDMA-induced locomotor stimulation and exploratory behavior suppression.
Main Methods:
- Assessed behavioral responses (locomotion, exploration) of 5-HT1B receptor knockout mice to MDMA.
- Administered MDMA to wild-type mice pretreated with a 5-HT1B/1D receptor antagonist (GR 127935).
- Compared behavioral outcomes between knockout/pretreated mice and wild-type controls.
Main Results:
- 5-HT1B receptor knockout mice exhibited a reduced, though delayed, locomotor response to MDMA.
- MDMA suppressed exploratory behavior in both knockout and wild-type mice.
- Pharmacological blockade of 5-HT1B/1D receptors attenuated MDMA-induced locomotion but did not prevent exploration suppression.
Conclusions:
- The 5-HT1B receptor is partially required for MDMA's locomotor stimulant effects.
- Mechanisms independent of the 5-HT1B receptor mediate MDMA's suppression of exploratory behavior.
- These findings elucidate the specific roles of 5-HT receptor subtypes in MDMA's complex behavioral pharmacology.