title: Khat (Catha edulis) and ethanol co-dependence modulate seizure expression in a pentylenetetrazol seizure model.
abstract: BACKGROUND
  Khat is a plant with psychostimulant properties whose parts, mainly leaves and twigs, are chewed for its euphoriant effects. Khat use and ethanol abuse are increasingly becoming global health concerns especially among many disadvantaged social groups. The present studies were undertaken to investigate seizure susceptibility and responses following chronic co-administration of khat and ethanol.
  
  
  METHODS
  Juvenile male Sprague-Dawley (SD) rats were administered khat, ethanol or combined khat and ethanol twice daily for 28 days by gavage. Khat-treated animals received 2 g/kg or 4 g/kg body weight continuously for the study period. Ethanol-treated animals received 20% ethanol at a dose of 4 g/kg body weight. The convulsant, pentylenetetrazol (PTZ), was administered intraperitoneally at a dose of 40 mg/kg body weight. Seizure responses were recorded.
  
  
  RESULTS
  Twice-daily dosing of khat did not produce inhibition of weight gain. Khat alone, combined khat and 20% ethanol, but not 20% ethanol alone, significantly reduced the latency to seize. Khat treatment at 2 g/kg but not 4 g/kg body weight also significantly increased the duration of seizures. Conversely, combined khat and ethanol reduced the duration of seizures compared to controls. Ethanol alone reduced the seizure severity while khat alone, and combined khat and ethanol, produced close to the maximum seizure severity.
  
  
  CONCLUSIONS
  These data suggest that combined moderate to high dose khat and ethanol co-dependence produce a greater deleterious CNS effect than either drug alone. Future studies will address neurochemical effects, in addition to neuroadaptations, resulting from coabuse of these drugs.
authors.affiliation: Department of Pharmacology and Therapeutics, Faculty of Medicine, Mbarara University of Science and Technology, PO Box 1410, Mbarara, Uganda. paulalele@must.ac.ug
authors.forename: Paul E
authors.initials: PE
authors.lastname: Alele
authors.forename: James B
authors.initials: JB
authors.lastname: Rujumba
mesh_terms: D000437:Alcoholism / Q000150:complications* / Q000503:physiopathology; D000818:Animals; D029754:Catha; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D000431:Ethanol / Q000633:toxicity*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010433:Pentylenetetrazole; D028321:Plant Preparations / Q000633:toxicity*; D011619:Psychotropic Drugs / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control; D013997:Time Factors
chemical_list: D028321:Plant Preparations; D011619:Psychotropic Drugs; D000431:Ethanol; D010433:Pentylenetetrazole