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Updated: May 9, 2026

Single Synapse Indicators of Glutamate Release and Uptake in Acute Brain Slices from Normal and Huntington Mice
Published on: March 11, 2020
Amphetamine stimulates movement through thalamocortical glutamate release
Omar S Mabrouk1, Daniel Z Semaan, Sarah Mikelman
1Department of Chemistry, University of Michigan, Ann Arbor, Michigan, USA; Department of Pharmacology, University of Michigan, Ann Arbor, Michigan, USA.
Amphetamine-induced hyperactivity in rats is mediated by thalamocortical signaling. Blocking ventrolateral thalamus input or cortical AMPA receptors significantly reduces this amphetamine (AMPH) effect.
Area of Science:
- Neuroscience
- Pharmacology
- Behavioral Science
Background:
- The ventrolateral thalamus (VL) is a key relay for basal ganglia and motor cortex communication.
- Amphetamine (AMPH) stimulates monoamine release and causes hyperlocomotion, but the underlying thalamocortical mechanisms are not fully understood.
Purpose of the Study:
- To investigate the role of ventrolateral thalamus (VL) projections to the primary motor cortex (M1) in amphetamine-induced hyperlocomotion.
- To identify the specific glutamate receptors involved in this thalamocortical pathway.
Main Methods:
- Dual probe microdialysis and locomotor behavior monitoring in rats.
- Pharmacological interventions including tetrodotoxin (TTX) in the VL and glutamate receptor antagonists (NBQX, MK-801) in the cortex.
- Ex vivo M1 tissue perfusion to assess local glutamate-dopamine interactions.
Main Results:
- Tetrodotoxin (TTX) perfusion in the VL significantly reduced AMPH-induced hyperactivity and associated cortical glutamate and monoamine release.
- Cortical application of AMPA/kainate receptor antagonist NBQX, and to a lesser extent NMDA receptor antagonist MK-801, attenuated AMPH-induced hyperactivity.
- Thalamocortical glutamate acting via cortical AMPA receptors is crucial for AMPH-induced hyperlocomotion.
Conclusions:
- Amphetamine (AMPH) generates hyperlocomotive states through thalamocortical signaling.
- Cortical AMPA receptors are essential mediators of AMPH-induced hyperlocomotion, highlighting the importance of the thalamocortical pathway in motor control modulation.
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