Regulation of GluA1 phosphorylation by d-amphetamine and methylphenidate in the cerebellum

Addict Biol. 2021 Jul;26(4):e12995. doi: 10.1111/adb.12995. Epub 2020 Dec 26.


Prescription stimulants, such as d-amphetamine or methylphenidate are used to treat suffering from attention-deficit hyperactivity disorder (ADHD). They potently release dopamine (DA) and norepinephrine (NE) and cause phosphorylation of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA1 in the striatum. Whether other brain regions are also affected remains elusive. Here, we demonstrate that d-amphetamine and methylphenidate increase phosphorylation at Ser845 (pS845-GluA1) in the membrane fraction of mouse cerebellum homogenate. We identify Bergmann glial cells as the source of pS845-GluA1 and demonstrate a requirement for intact NE release. Consequently, d-amphetamine-induced pS845-GluA1 was prevented by β1-adenoreceptor antagonist, whereas the blockade of DA D1 receptor had no effect. Together, these results indicate that NE regulates GluA1 phosphorylation in Bergmann glial cells in response to prescription stimulants.

Keywords: Bergmann glial cells; GluA1; cerebellar cortex; monoaminergic system; prescription stimulants.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Central Nervous System Stimulants / pharmacology*
  • Cerebellum / metabolism*
  • Dextroamphetamine / pharmacology*
  • Male
  • Methylphenidate / pharmacology*
  • Mice
  • Norepinephrine / metabolism
  • Phosphorylation
  • Phosphotransferases*
  • Receptors, Dopamine D1 / metabolism


  • Central Nervous System Stimulants
  • Receptors, Dopamine D1
  • Methylphenidate
  • Phosphotransferases
  • Dextroamphetamine
  • Norepinephrine