Abstract
Drugs of abuse activate the reward circuitry of the mesocorticolimbic system, and it has been hypothesized that drug exposure triggers synaptic plasticity of glutamatergic synapses onto dopamine (DA) neurons of the ventral tegmental area. Here, we show that just a 2 h in vivo exposure to amphetamine is sufficient to potentiate these synapses, measured as an increase in the synaptic AMPAR/NMDAR ratio. We tested the prediction that an increase in GluR1-containing AMPA receptors would result in an increase in GluR1 homomeric receptors at synapses, but were unable to observe any evidence of the predicted rectification in DA neurons from animals treated with amphetamine. We also examined the possibility of increased AMPA receptor insertion in the membrane, but did not detect a significant increase in biotinylated surface GluR1. We conclude that amphetamine induces rapid changes in synaptic AMPAR/NMDAR ratios, suggesting that potentiation of glutamatergic synapses is a relatively early event in the series of neuroadaptations in response to drugs of abuse.
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Acknowledgements
We thank Drs M Bear, BJ Yoon, J Whitlock, J Marshall, L Needleman, N Riley, Z Ren, A Zhitkovich, M Reynolds, and L Gabel for providing reagents, equipment, and technical expertise, and Drs J Edwards, E Penick, and F Salmanzadeh for helpful comments on the manuscript. This work was supported by grants from NARSAD and NIH DA11289 to JAK, DA15588 to LJF.
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Faleiro, L., Jones, S. & Kauer, J. Rapid Synaptic Plasticity of Glutamatergic Synapses on Dopamine Neurons in the Ventral Tegmental Area in Response to Acute Amphetamine Injection. Neuropsychopharmacol 29, 2115–2125 (2004). https://doi.org/10.1038/sj.npp.1300495
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DOI: https://doi.org/10.1038/sj.npp.1300495
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