title: Baclofen and gamma-hydroxybutyrate differentially altered behavior, EEG activity and sleep in rats.
abstract: OBJECTIVE
  Animal and human studies have shown that sleep may have an impact on functional recovery after brain damage. Baclofen (Bac) and gamma-hydroxybutyrate (GHB) have been shown to induce physiological sleep in humans, however, their effects in rodents are unclear. The aim of this study is to characterize sleep and electroencelphalogram (EEG) after Bac and GHB administration in rats. We hypothesized that both drugs would induce physiological sleep.
  
  
  METHODS
  Adult male Sprague-Dawley rats were implanted with EEG/electromyogram (EMG) electrodes for sleep recordings. Bac (10 or 20 mg/kg), GHB (150 or 300 mg/kg) or saline were injected 1 h after light and dark onset to evaluate time of day effect of the drugs. Vigilance states and EEG spectra were quantified.
  
  
  RESULTS
  Bac and GHB induced a non-physiological state characterized by atypical behavior and an abnormal EEG pattern. After termination of this state, Bac was found to increase the duration of non-rapid eye movement (NREM) and rapid eye movement (REM) sleep (∼90 and 10 min, respectively), reduce sleep fragmentation and affect NREM sleep episode frequency and duration (p<0.05). GHB had no major effect on vigilance states. Bac drastically increased EEG power density in NREM sleep in the frequencies 1.5-6.5 and 9.5-21.5 Hz compared to saline (p<0.05), while GHB enhanced power in the 1-5-Hz frequency band and reduced it in the 7-9-Hz band. Slow-wave activity in NREM sleep was enhanced 1.5-3-fold during the first 1-2 h following termination of the non-physiological state. The magnitude of drug effects was stronger during the dark phase.
  
  
  CONCLUSIONS
  While both Bac and GHB induced a non-physiological resting state, only Bac facilitated and consolidated sleep, and promoted EEG delta oscillations thereafter. Hence, Bac can be considered a sleep-promoting drug and its effects on functional recovery after stroke can be evaluated both in humans and rats.
authors.affiliation: Center for Experimental Neurology (ZEN), Department of Neurology, Inselspital, Bern University Hospital, Switzerland. Electronic address: Aleksandra.Hodor@access.uzh.ch.
authors.forename: A
authors.initials: A
authors.lastname: Hodor
authors.affiliation: Center for Experimental Neurology (ZEN), Department of Neurology, Inselspital, Bern University Hospital, Switzerland.
authors.forename: S
authors.initials: S
authors.lastname: Palchykova
authors.affiliation: Center for Experimental Neurology (ZEN), Department of Neurology, Inselspital, Bern University Hospital, Switzerland.
authors.forename: B
authors.initials: B
authors.lastname: Gao
authors.affiliation: Center for Experimental Neurology (ZEN), Department of Neurology, Inselspital, Bern University Hospital, Switzerland.
authors.forename: C L
authors.initials: CL
authors.lastname: Bassetti
mesh_terms: D000759:Adjuvants, Anesthesia / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D058256:Brain Waves / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004576:Electromyography; D058786:GABA-B Receptor Agonists / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects*; D012978:Sodium Oxybate / Q000494:pharmacology*
chemical_list: D000759:Adjuvants, Anesthesia; D058786:GABA-B Receptor Agonists; D012978:Sodium Oxybate; D001418:Baclofen
keywords: Baclofen; EEG; GHB; rats; sleep