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Updated: Mar 10, 2026
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A General Method for Evaluating Deep Brain Stimulation Effects on Intravenous Methamphetamine Self-Administration
Published on: January 22, 2016
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Amphetamine and Methamphetamine Increase NMDAR-GluN2B Synaptic Currents in Midbrain Dopamine Neurons
Ming-Hua Li1, Suzanne M Underhill2, Cheryl Reed3
1Department of Neurological Surgery, Oregon Health & Science University, Portland, OR, USA.
Summary
Amphetamine and methamphetamine acutely enhance NMDA receptor currents in dopamine neurons by activating GluN2B receptors. This potentiation, mediated by the dopamine transporter and EAAT3, reduces psychostimulant-induced hyperactivity.
Area of Science:
- Neuroscience
- Pharmacology
- Molecular Biology
Background:
- Amphetamine (AMPH) and methamphetamine (MA) are widely abused psychostimulants.
- Their acute effects on dopamine neuron signaling are not fully understood.
Purpose of the Study:
- To investigate the mechanisms by which AMPH and MA modulate NMDA receptor (NMDAR) and AMPA receptor (AMPAR) function in midbrain dopamine neurons.
- To identify the specific receptor subunits and transporters involved in these modulations.
Main Methods:
- Electrophysiological recordings in midbrain dopamine neurons.
- Application of specific receptor inhibitors (GluN2B antagonists, NMDAR blocker) and transporter inhibitors.
- Behavioral studies measuring locomotor activity in response to MA and GluN2B inhibitors.
Main Results:
- AMPH and MA acutely increase NMDAR-mediated currents and decrease AMPAR/NMDAR ratios.
- This potentiation is dependent on AMPH transport via the dopamine transporter and involves GluN2B-containing NMDARs.
- Inhibition of EAAT3 internalization blocks potentiation, suggesting increased extracellular glutamate.
- Potentiated NMDARs are located on the plasma membrane.
- GluN2B inhibitors reduce MA-induced locomotor activity.
Conclusions:
- Acute psychostimulant administration potentiates NMDAR currents in dopamine neurons through GluN2B activation.
- This mechanism involves dopamine transporter, EAAT3, and extracellular glutamate.
- Targeting GluN2B receptors may offer a therapeutic strategy for psychostimulant abuse.
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