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Psychopharmacology (Berl). 2004 May;173(3-4):310-7. Epub 2004 Jan 28.

MDMA "ecstasy" alters hyperactive and perseverative behaviors in dopamine transporter knockout mice.

Author information

1
Department of Psychiatry 0804, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.

Abstract

RATIONALE:

Mice lacking the gene for the dopamine transporter (DAT) show a unique behavioral phenotype characterized by locomotor hyperactivity and repetitive circling in a novel environment. The hyperactivity of DAT (-/-) mice can be attenuated by psychostimulants and by serotonin uptake inhibitors, suggesting an important role for serotonin in the attenuation of locomotor hyperactivity in these mice.

OBJECTIVES:

These studies characterized the effects of 3,4-methylenedioxy-N-methylamphetamine (MDMA), a serotonin releaser, on the amount and patterns of locomotor activity in DAT (+/+) and (-/-) mice. We compared the locomotor patterns produced by MDMA to those observed in DAT (-/-) mice, and examined whether MDMA altered the hyperactivity and perseverative locomotor patterns in DAT (-/-) mice.

METHODS:

The effects of MDMA (10, 30 mg/kg) on locomotor activity in DAT (+/+) mice were measured for 90 min in a video tracker system to determine the optimal dose for subsequent studies in DAT (+/+) and (-/-) mice. The effects of 20 mg/kg MDMA on patterns of locomotor activity in DAT (+/+) and (-/-) mice were measured for 90 min.

RESULTS:

In DAT (+/+) mice, MDMA increased locomotor activity and induced repetitive straight movement patterns. In DAT (-/-) mice, however, MDMA (20 mg/kg) attenuated the characteristic locomotor hyperactivity seen in these mice. In contrast, MDMA potentiated the thigmotaxis and decreased entropy observed in the DAT (-/-) mice.

CONCLUSIONS:

The effects of MDMA observed here demonstrate that the different aspects of the abnormal locomotor behavior exhibited by DAT (-/-) mice can be independently manipulated by pharmacological treatments.

PMID:
14747902
DOI:
10.1007/s00213-003-1765-7
[Indexed for MEDLINE]

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