Chronic pregabalin treatment decreases excitability of dentate gyrus and accelerates maturation of adult-born granule cells

J Neurochem. 2017 Jan;140(2):257-267. doi: 10.1111/jnc.13740. Epub 2016 Sep 9.

Abstract

Pregabalin (PGB) is extensively prescribed to treat neurological and neuropsychiatrical conditions such as neuropathic pain, anxiety disorders, and epilepsy. Although PGB is known to bind selectively to the α2δ subunit of voltage-gated calcium channels, there is little understanding about how it exerts its therapeutic effects. In this article, we analyzed the effects of an in vivo chronic treatment with PGB over the physiology of dentate gyrus granule cells (DGGCs) using ex vivo electrophysiological and morphological analysis in adult mice. We found that PGB decreases neuronal excitability of DGGCs. In addition, PGB accelerates maturation of adult-born DGGCs, an effect that would modify dentate gyrus plasticity. Together, these findings suggest that PGB reduces activity in the dentate gyrus and modulates overall network plasticity, which might contribute to its therapeutic effects. Cover Image for this issue: doi: 10.1111/jnc.13783.

Keywords: Gabapentin; Pregabalin; dentate gyrus; neurogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Calcium Channels / drug effects*
  • Calcium Channels / metabolism
  • Cytoplasmic Granules / drug effects
  • Cytoplasmic Granules / metabolism
  • Dentate Gyrus / drug effects*
  • Dentate Gyrus / physiology
  • Epilepsy / drug therapy
  • Mice, Inbred C57BL
  • Neuralgia / drug therapy*
  • Neurons / drug effects*
  • Neurons / metabolism
  • Pregabalin / administration & dosage
  • Pregabalin / pharmacology*
  • gamma-Aminobutyric Acid / pharmacology

Substances

  • Calcium Channels
  • Pregabalin
  • gamma-Aminobutyric Acid