Electrophysiologic changes in ventral midbrain dopaminergic neurons resulting from (+/-) -3,4-methylenedioxymethamphetamine (MDMA-"Ecstasy").
Mauro Federici, Luca Sebastianelli, Silvia Natoli, Giorgio Bernardi, Nicola B Mercuri
Biological Psychiatry September 15, 2007 DOI: 10.1016/j.biopsych.2006.11.019 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | In vitro electrophysiological study Peer reviewed |
|---|---|
| Population | Dopaminergic neurons in ventral midbrain slices |
| Intervention | MDMA |
| Dose | 1 micromol/L, 3 micromol/L, 10-30 micromol/L |
| Topics | MDMA |
| Key points | MDMA inhibits dopaminergic neurons at 3-30 micromol/L via indirect activation of D2 autoreceptors resulting from increased extracellular dopamine, while at 1-3 micromol/L it can excite cells partly through reduction of the GABA(B) IPSP. Excitatory effects involve 5-HT1B receptors and inhibitory effects involve D2 receptors. |
Abstract
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. We examined the actions of MDMA on intracellularly recorded dopaminergic neurons maintained in slices. At 1 micromol/L, MDMA depolarized and excited the cells; at 3 micromol/L, either excited or inhibited the neurons. Interestingly, higher concentrations (10-30 micromol/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 GABA(B) IPSP by activating 5-HT 1B receptors. Our data demonstrate that 3-30 micromol/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 GABA(B) IPSP could partially account for excitation caused by 1-3 micromol/L drug.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
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- Role of Serotonin via 5-HT2B Receptors in the Reinforcing Effects of MDMA in Mice PLoS One November 20, 2009
- PRECLINICAL STUDY: Changes in leptin, ghrelin, growth hormone and neuropeptide‐Y after an acute model of MDMA and methamphetamine exposure in rats Addiction Biology October 2, 2007
- 5-HT2C receptors in the nucleus accumbens constrain the rewarding effects of MDMA. bioRxiv : the preprint server for biology October 22, 2024
- MDMA (3,4-methylenedioxy-methamphetamine) Drug Addiction Mechanisms in the Brain April 8, 2024
- 3,4-Methylenedioxymethamphetamine (MDMA) Alters Synaptic Dopamine Release in the Dorsal Striatum Through Nicotinic Receptors and DAT Inhibition. Neuroscience May 1, 2018
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Cites 13
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