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Updated: Dec 30, 2025
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Single Cell Measurement of Dopamine Release with Simultaneous Voltage-clamp and Amperometry
Published on: November 21, 2012
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Methamphetamine increases dopamine release in the nucleus accumbens through calcium-dependent processes
Jordan T Yorgason1, David M Hedges2, J Daniel Obray1
1Department of Psychology/Neuroscience, Brigham Young University, 1050 SWKT, Provo, UT, 84602, USA.
Psychopharmacology
|January 23, 2020
Summary
Methamphetamine (METH) increases dopamine release via intracellular calcium. Blocking this calcium release prevents METH
Area of Science:
- Neuroscience
- Pharmacology
- Cell Biology
Background:
- Methamphetamine (METH) enhances dopamine (DA) signaling in brain regions like the nucleus accumbens (NAc).
- Sigma receptor activation, which can be triggered by METH, leads to intracellular calcium release, potentially mediating METH's effects on DA.
- Previous research suggests blocking sigma receptors inhibits METH-induced DA increases.
Purpose of the Study:
- To investigate the specific roles of intracellular and extracellular calcium in METH-induced dopamine release and associated behaviors.
- To determine if blocking intracellular calcium release can prevent METH's effects on dopamine signaling and behavior.
Main Methods:
- Ratiometric calcium imaging in human neural progenitor cell-derived DA cells to measure METH-induced calcium release.
- Fast-scan cyclic voltammetry in mouse brain slices to assess METH's impact on electrically stimulated and DAT-mediated DA efflux.
- Pharmacological manipulation of calcium levels using channel blockers (Cd2+, IP3-sensitive channels), intracellular chelators (BAPTA-AM), and zero-calcium solutions.
- Behavioral testing in rats involving intra-NAc injections of an IP3 receptor blocker (2-APB) or vehicle before METH administration to assess locomotor activity.
Main Results:
- Reducing extracellular calcium and blocking intracellular calcium stores inhibited METH-induced intracellular calcium release.
- Intracellular calcium chelation and blockade of intracellular calcium release attenuated METH's effects on voltammetric measures of dopamine.
- Blocking intracellular calcium release with 2-APB enhanced METH-induced circling behavior in rats.
Conclusions:
- Methamphetamine triggers dopamine release in the nucleus accumbens primarily through intracellular calcium signaling pathways.
- Interfering with intracellular calcium release effectively blocks METH's influence on dopamine signals and related behavioral responses.
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