title: Methamphetamine self-administration modulates glutamate neurophysiology.
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.
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC, 29425, USA.
authors.forename: Devesh
authors.initials: D
authors.lastname: Mishra
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC, 29425, USA.
authors.forename: Jose Ignacio
authors.initials: JI
authors.lastname: Pena-Bravo
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC, 29425, USA.
authors.forename: Kah-Chung
authors.initials: KC
authors.lastname: Leong
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC, 29425, USA.
authors.forename: Antonieta
authors.initials: A
authors.lastname: Lavin
authors.affiliation: Department of Neurosciences, Medical University of South Carolina, 173 Ashley Avenue, Charleston, SC, 29425, USA. reichel@musc.edu.
authors.forename: Carmela M
authors.initials: CM
authors.lastname: Reichel
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects*; D005108:Extinction, Psychological / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D013569:Synapses / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000697:Central Nervous System Stimulants; D018698:Glutamic Acid; D008694:Methamphetamine
keywords: AMPA/NMDA; Corticostriatal circuitry; Methamphetamine; Paired pulse ratio; Protein expression; Self-administration