The GABAA agonist THIP (gaboxadol) increases non-REM sleep and enhances delta activity in the rat

Neuroreport. 1996 Sep 2;7(13):2241-5. doi: 10.1097/00001756-199609020-00036.

Abstract

To investigate the effects of the selective gamma-aminobutyric acid (GABA)A receptor agonist 4,5,6,7-tetrahydroisoxazolo (5,4-c)pyridin-3-ol (THIP) on sleep, vehicle or 2 or 4 mg kg-1 of THIP were randomly administered i.p. to 8 rats at light onset. EEG and EMG were recorded during the first 6 hours after injection. THIP 4 mg kg-1 transiently evoked bursts of absence epilepsy-like EEG hypersynchronization. It significantly promoted non-rapid eye movement (non-REM) sleep and elevated delta activity within non-REM sleep. This was accompanied by an increase in both the rise rate and maximal level of delta activity within the non-REM sleep episodes. The effects of THIP on sleep resemble those reported earlier for the GABAA agonist muscimol and are dissimilar from those induced by benzodiazepine-agonistic modulators of GABAA receptors. These data indicate that agonists and agonistic modulators of GABAA receptors affect sleep differentially.

MeSH terms

  • Animals
  • Delta Rhythm / drug effects*
  • Electroencephalography / drug effects
  • Electromyography / drug effects
  • GABA Agonists / pharmacology*
  • GABA-A Receptor Agonists
  • Isoxazoles / pharmacology*
  • Male
  • Rats
  • Rats, Wistar
  • Sleep Stages / drug effects*
  • Sleep, REM / drug effects
  • Wakefulness / drug effects

Substances

  • GABA Agonists
  • GABA-A Receptor Agonists
  • Isoxazoles
  • gaboxadol