Background
Although dopamine (DA) has been implicated in the psychostimulant properties of 3,4-methylenedioxymethamphetamine
(MDMA), there is no detailed information on its modalities of action on single ventral
midbrain dopaminergic neurons.
Methods
We examined the actions of MDMA on intracellularly recorded dopaminergic neurons maintained
in slices.
Results
At 1 μmol/L, MDMA depolarized and excited the cells; at 3 μmol/L, either excited or
inhibited the neurons. Interestingly, higher concentrations (10–30 μmol/L) inhibited
firing through membrane hyperpolarization or caused an outward current. Whereas MDMA’s
excitatory effects were antagonized by pindolol, indicating involvement of 5-HT 1B
receptors, the inhibitory effects were counteracted by sulpiride indicating involvement
D2 receptors. Treatment of the cells with carbidopa eliminated MDMA-induced firing
inhibition and membrane hyperpolarization. MDMA enhanced DA-induced cellular responses
but reduced those of amphetamine. Cocaine-induced outward currents were not affected
by MDMA. These actions are consistent with inhibition of the DA transporter. Moreover,
MDMA depressed the GABAB IPSP by activating 5-HT 1B receptors.
Conclusions
Our data demonstrate that 3–30 μmol/L MDMA preferentially inhibits the dopaminergic
cells via indirect activation of D2 autoreceptors due to increased extracellular concentration
of DA. In contrast, reduction of the GABAB IPSP could partially account for excitation caused by 1–3 μmol/L drug.
Key Words
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Article info
Publication history
Published online: May 21, 2007
Accepted:
November 28,
2006
Received in revised form:
November 16,
2006
Received:
October 4,
2006
Identification
Copyright
© 2007 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
