Methamphetamine self-administration modulates glutamate neurophysiology

Brain Struct Funct. 2017 Jul;222(5):2031-2039. doi: 10.1007/s00429-016-1322-x. Epub 2016 Oct 5.

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.

Keywords: AMPA/NMDA; Corticostriatal circuitry; Methamphetamine; Paired pulse ratio; Protein expression; Self-administration.

MeSH terms

  • Animals
  • Central Nervous System Stimulants / pharmacology
  • Excitatory Postsynaptic Potentials / drug effects*
  • Extinction, Psychological / drug effects
  • Glutamic Acid / metabolism*
  • Male
  • Methamphetamine / administration & dosage
  • Methamphetamine / pharmacology*
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Prefrontal Cortex / drug effects
  • Prefrontal Cortex / metabolism
  • Rats, Sprague-Dawley
  • Self Administration
  • Synapses / drug effects*
  • Synapses / metabolism

Substances

  • Central Nervous System Stimulants
  • Glutamic Acid
  • Methamphetamine