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


OBJECTIVE
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.
Powell
Susan B
SB
Department of Psychiatry 0804, University of California San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
Lehmann-Masten
Virginia D
VD
Paulus
Martin P
MP
Gainetdinov
Raul R
RR
Caron
Marc G
MG
Geyer
Mark A
MA
D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D050483:Dopamine Plasma Membrane Transport Proteins; D005260:Female; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency* / Q000235:genetics; D026901:Membrane Transport Proteins / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D009043:Motor Activity / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D018490:Serotonin Agents / Q000494:pharmacology*
D000697:Central Nervous System Stimulants; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D018490:Serotonin Agents; C493215:Slc6a3 protein, mouse; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine