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MDMA "ecstasy" alters hyperactive and perseverative behaviors in dopamine transporter knockout mice
Susan B Powell1, Virginia D Lehmann-Masten, Martin P Paulus
1Department of Psychiatry 0804, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Psychopharmacology
|January 30, 2004
Summary
Mice lacking the dopamine transporter (DAT) exhibit hyperactivity, which 3,4-methylenedioxy-N-methylamphetamine (MDMA) can reduce. MDMA also altered specific movement patterns in these mice, showing distinct effects on hyperactivity and stereotypy.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- Mice lacking the dopamine transporter (DAT) display hyperactivity and repetitive circling in novel environments.
- Serotonin uptake inhibitors can attenuate this hyperactivity, suggesting a role for serotonin.
Purpose of the Study:
- To investigate the effects of 3,4-methylenedioxy-N-methylamphetamine (MDMA), a serotonin releaser, on locomotor activity in DAT (+/+) and (-/-) mice.
- To compare MDMA-induced locomotor patterns with those of DAT (-/-) mice and assess MDMA's impact on hyperactivity and perseverative behaviors.
Main Methods:
- Determined optimal MDMA dose (10, 30 mg/kg) in DAT (+/+) mice using a video tracker system.
- Measured the effects of 20 mg/kg MDMA on locomotor activity patterns in DAT (+/+) and (-/-) mice over 90 minutes.
Main Results:
- In DAT (+/+) mice, MDMA increased locomotor activity and induced repetitive straight-line movements.
- MDMA (20 mg/kg) attenuated hyperactivity in DAT (-/-) mice but potentiated thigmotaxis and decreased movement entropy.
Conclusions:
- Pharmacological interventions, such as MDMA, can independently modulate different aspects of abnormal locomotor behavior in DAT (-/-) mice.
- These findings highlight the complex interplay between dopamine transporter function and serotonin systems in regulating motor activity.