title: Effects of an alkaloid-rich extract from Mitragyna speciosa leaves and fluoxetine on sleep profiles, EEG spectral frequency and ethanol withdrawal symptoms in rats.
abstract: BACKGROUND
  Many antidepressants are effective in alleviating ethanol withdrawal symptoms. However, most of them suppress rapid eye movement (REM) sleep. Thus, development of antidepressants without undesirable side effects would be preferable. Previously, crude alkaloid extract from Mitragyna speciosa (MS) Korth was found to produce antidepressant activities. It was hypothesized that the alkaloid extract from MS may attenuate ethanol withdrawal without REM sleep disturbance.
  
  
  METHODS
  Adult male Wistar rats implanted with electrodes over the frontal and parietal cortices were used for two separated studies. For an acute study, 10 mg/kg fluoxetine or 60 mg/kg alkaloid extract from MS were administered intragastrically. Electroencephalographic (EEG) signals were recorded for 3 h to examine sleep profiles and EEG fingerprints. Another set of animal was used for an ethanol withdrawal study. They were rendered dependent on ethanol via a modified liquid diet (MLD) containing ethanol ad libitum for 28 days. On day 29, fluoxetine (10 mg/kg) or alkaloid extract from MS (60 mg/kg) were administered 15 min before the ethanol-containing MLD was replaced with an isocaloric ethanol-free MLD to induced ethanol withdrawal symptoms.
  
  
  RESULTS
  The sleep analysis revealed that alkaloid extract from MS did not change any REM parameters which included average duration of each REM episode, total REM time, number of REM episode and REM latency whereas fluoxetine significantly suppressed all REM parameters and delayed REM latency. However, power spectral analysis revealed similar fingerprints for fluoxetine and alkaloid extract from MS characterized by decreasing powers in the slow frequency range in frontal and parietal cortical EEG. Neither treatment affected spontaneous motor activity. Finally, both alkaloid extract from MS and fluoxetine were found to significantly attenuate ethanol withdrawal-induced hyperexcitability (increases gamma activity) in both cortices and to reduce locomotor activity.
  
  
  CONCLUSIONS
  The present study demonstrated that the alkaloid extract from MS alleviates ethanol withdrawal severity with no side effect on REM sleep. In addition, these data suggest that suppressive effects on slow frequency powers but not REM sleep may be hallmarks of effective antidepressants for ethanol withdrawal treatment.
authors.affiliation: Department of Physiology, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand. Electronic address: dcheaha@gmail.com.
authors.forename: Dania
authors.initials: D
authors.lastname: Cheaha
authors.affiliation: Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand.
authors.forename: Niwat
authors.initials: N
authors.lastname: Keawpradub
authors.affiliation: Department of Pharmacology, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand.
authors.forename: Kitja
authors.initials: K
authors.lastname: Sawangjaroen
authors.affiliation: Scientific Equipment Center, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand.
authors.forename: Pimpimol
authors.initials: P
authors.lastname: Phukpattaranont
authors.affiliation: Department of Physiology, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand; The Natural Product Research Center of Excellence, Faculty of Science, Prince of Songkla University, Hatyai, Songkhla 90112, Thailand. Electronic address: Kumarnsit.e@gmail.com.
authors.forename: Ekkasit
authors.initials: E
authors.lastname: Kumarnsit
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D004566:Electrodes; D004569:Electroencephalography; D000431:Ethanol / Q000009:adverse effects; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D032065:Mitragyna / Q000737:chemistry*; D010936:Plant Extracts / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012895:Sleep, REM / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy*
chemical_list: D000470:Alkaloids; D010936:Plant Extracts; D005473:Fluoxetine; D000431:Ethanol
keywords: EEG; Ethanol withdrawal; Fluoxetine; Mitragyna speciosa; REM