Abstract
World-wide methamphetamine (meth) use is increasing at a rapid rate; therefore, it has become increasingly important to understand the synaptic changes and neural mechanisms affected by drug exposure. In rodents, 6-h access to contingent meth results in an escalation of drug intake and impaired cognitive sequelae typically associated with changes within the corticostriatal circuitry. There is a dearth of knowledge regarding the underlying physiological changes within this circuit following meth self-administration. We assessed pre- and postsynaptic changes in glutamate transmission in the medial prefrontal cortex (mPFC) and nucleus accumbens (NAc) following daily 6-h meth self-administration. In the mPFC, meth caused postsynaptic adaptations in ionotropic glutamate receptor distribution and function, expressed as a decrease in AMPA/NMDA ratio. This change was driven by an increase in NMDA receptor currents and an increase in GluN2B surface expression. In the NAc, meth decreased the paired-pulse ratio and increased the frequency of spontaneous excitatory postsynaptic currents with no indication of postsynaptic changes. These changes in mPFC synapses and NAc activity begin to characterize the impact of meth on the corticostriatal circuitry.
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Acknowledgments
We would like to thank Shannon Ghee and Carole Berini for technical assistance and Dr. John Dinolfo of the Writing Center at the Medical University of South Carolina for editing the final version of the manuscript.
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This project was funded by NIH/NIDA grant R01DA033049 to CMR and Hjarnfonden Brain Foundation of Sweden to DM.
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The authors declare that they have no conflicts of interest.
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D. Mishra and J. I. Pena-Bravo contributed equally.
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Mishra, D., Pena-Bravo, J.I., Leong, KC. et al. Methamphetamine self-administration modulates glutamate neurophysiology. Brain Struct Funct 222, 2031–2039 (2017). https://doi.org/10.1007/s00429-016-1322-x
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DOI: https://doi.org/10.1007/s00429-016-1322-x