Effect of gabapentin on sleep patterns disturbed by epilepsy

Epilepsy Behav. 2019 Mar:92:290-296. doi: 10.1016/j.yebeh.2018.12.012. Epub 2019 Feb 4.

Abstract

For a long time, numerous sleep alterations induced by nocturnal epilepsy have been described. Such alterations include sleep fragmentation, decrement of sleep efficiency, increment of the wake time after sleep onset (WASO), increment of light sleep, and decrement of sleep depth. On the other hand, gabapentin (GBP), an antiepileptic drug analog of γ-aminobutyric acid (GABA) used as adjunctive and eventually, as a monotherapeutic treatment, induces a significant improvement in patients with both focal and secondarily generalized partial seizures. In experimental epilepsy models, this drug protects against pentylenetetrazol (PTZ)-induced convulsions. In consideration of such GBP properties, the aim of this work was to investigate its efficacy to protect against sleep disturbances provoked by convulsive seizures induced by the administration of PTZ. Nine-hour (9-hour) polygraphic studies were carried out in chronically implanted male adult Wistar rats separated into 4 different groups of 6 individuals. Control recordings in each group were done after saline administration. One group received a SC Subcutaneous (SC) injection of 50 mg/kg of PTZ alone while the other three groups were injected with either 15, 30, or 60 mg/kg IP Intraperitoneal (IP) of GBP 30 min prior to PTZ (50 mg/kg SC) administration. Animals displayed the whole range of electrophysiological and behavioral manifestations of the disease during the epileptic episodes induced by PTZ administration, and the states of vigilance were significantly altered. Insomnia occurred immediately after PTZ injection preceding the appearance of the first epileptic symptoms. Thus, both slow wave sleep (SWS) and rapid eye movement sleep (REM sleep) were completely inhibited during a relatively long period of time. The disturbing effects of epilepsy on sleep decreased when animals were under GBP treatment. Improvement of sleep was dependent on the administered dose of this antiepileptic drug.

Keywords: Convulsive seizures; Gabapentin; REM sleep; Slow wave sleep; Wakefulness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology
  • Anticonvulsants / therapeutic use*
  • Dose-Response Relationship, Drug
  • Electrooculography / methods
  • Epilepsy / drug therapy*
  • Epilepsy / physiopathology*
  • Gabapentin / pharmacology
  • Gabapentin / therapeutic use*
  • Male
  • Polysomnography / methods
  • Rats
  • Rats, Wistar
  • Sleep / drug effects
  • Sleep / physiology
  • Sleep Wake Disorders / drug therapy*
  • Sleep Wake Disorders / physiopathology*
  • Wakefulness / drug effects
  • Wakefulness / physiology

Substances

  • Anticonvulsants
  • Gabapentin