Amphetamine stimulates movement through thalamocortical glutamate release
Article first published online: 19 AUG 2013
© 2013 International Society for Neurochemistry
Journal of Neurochemistry
Volume 128, Issue 1, pages 152–161, January 2014
How to Cite
J. Neurochem. (2014) 128, 152–161.
- Issue published online: 17 DEC 2013
- Article first published online: 19 AUG 2013
- Accepted manuscript online: 26 JUL 2013 01:08AM EST
- Manuscript Accepted: 23 JUL 2013
- Manuscript Revised: 11 JUL 2013
- Manuscript Received: 28 JUN 2013
- National Institute on Drug Abuse T32 training grant. Grant Numbers: DA07268, R37 EB003320, R01 DA11697
- National Institute for General Medicine. Grant Number: T32 GM007767
- National Center for Advancing Translational Sciences of the National Institutes of Health. Grant Number: 2UL1TR000433
- motor cortex;
The ventrolateral thalamus (VL) is a primary relay point between the basal ganglia and the primary motor cortex (M1). Using dual probe microdialysis and locomotor behavior monitoring, we investigated the contribution of VL input into M1 during amphetamine (AMPH)-stimulated monoamine release and hyperlocomotion in rats. Tetrodotoxin (10 μM) perfusion into the VL significantly lowered hyperactivity induced by AMPH (1 mg/kg i.p.). This behavioral response corresponded to reduced cortical glutamate and monoamine release. To determine which glutamate receptors the thalamocortical projections acted upon, we perfused either the α-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid (AMPA)/kainate receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX) (10 μM) or the N-methyl-D-aspartic acid (NMDA) receptor antagonist (MK-801) intracortically followed by systemic AMPH. The results show that AMPA/kainate, and to a lesser extent NMDA receptors, mediated the observed effects. As glutamate–monoamine interactions could possibly occur through local or circuit-based mechanisms, we isolated and perfused M1 tissue ex vivo to determine the extent of local glutamate–dopamine interactions. Taken together, these results demonstrate that AMPH generates hyperlocomotive states via thalamocortical signaling and that cortical AMPA receptors are an important mediator of these effects.
This study utilizes dual probe microdialysis sampling and comprehensive LC-MS analysis to determine the effects of amphetamine (1 mg/kg i.p.) on thalamocortical neurotransmission. Using pharmacological tools such as local thalamic tetrodotoxin (TTX) perfusion and glutamate antagonist at the cortical level, we demonstrate that thalamocortical glutamate (acting primarily through cortical AMPA receptors) is an essential component in amphetamine-induced hyperlocomotion.