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The Modulation of Gamma Oscillations by Methamphetamine in Rat Hippocampal Slices

Yanan Li1,2, Xin'e Xie2, Hang Xing2,3

  • 1The Second Affiliated Hospital, Xinxiang Medical University, Xinxiang, China.

Frontiers in Cellular Neuroscience
|July 9, 2019
PubMed

Insights

Methamphetamine (MA) enhances gamma (γ) oscillations, crucial for cognition. Researchers found that blocking dopamine and NMDA receptors, and inhibiting the Akt kinase, prevented this MA effect, revealing key cellular mechanisms.

Area of Science:

  • Neuroscience
  • Psychopharmacology
  • Cellular mechanisms

Background:

  • Gamma frequency oscillations (γ, 30-100 Hz) are vital for cognitive and motor functions.
  • Methamphetamine (MA) enhances brain γ oscillations, linked to psychomotor changes.
  • The precise cellular mechanisms underlying MA's modulation of γ oscillations remain unclear.

Purpose of the Study:

  • To investigate the cellular mechanisms by which MA modulates γ oscillations.
  • To explore the role of intracellular kinases in MA's enhancement of γ oscillations.
  • To elucidate the pathway involved in MA's effects on γ oscillations in the hippocampus.

Main Methods:

  • Utilized rat ventral hippocampal slices (area CA3) and kainate-induced γ oscillations.
  • Administered antagonists for dopamine receptor type 1 and 2 (DR1/DR2) and N-methyl-D-aspartate receptors (NMDAR).
  • Tested inhibitors for various intracellular kinases, including PKB/Akt, Protein Kinase A, phosphoinositide 3-kinase, and extracellular signal-related kinases.

Main Results:

  • DR1/DR2 antagonists, PKB/Akt inhibitor, and NMDAR antagonists blocked MA's enhancement of γ oscillations.
  • None of the tested antagonists or inhibitors affected baseline γ oscillation strength.
  • Inhibitors of Protein Kinase A, phosphoinositide 3-kinase, and extracellular signal-related kinases did not impact MA's effect on γ oscillations.

Conclusions:

  • The dopamine receptor (DR1/DR2)-Akt-NMDAR pathway is critical for MA-induced enhancement of γ oscillations.
  • This study offers new insights into the acute cellular mechanisms of MA's effects on psychosis.
  • Understanding these pathways may inform strategies for managing MA-induced neurological alterations.
Keywords:
Akt/PKBDRNMDARhippocampusmethamphetamineγ oscillation

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