title: Consequences of prolonged caffeine administration and its withdrawal on pilocarpine- and kainate-induced seizures in rats.
abstract: OBJECTIVE
  To investigate the consequences of caffeine consumption on epileptic seizures, we used the pilocarpine and the kainate models of epilepsy. We hypothesized that prolonged caffeine consumption or its withdrawal would alter adenosine levels and hence alter seizure susceptibility.
  
  
  METHODS
  We administered a 0.1% caffeine solution in the drinking water of adult male Wistar rats over a 2-week period. We challenged another group of animals with the same doses of pilocarpine or kainate 12 h after the withdrawal of the same caffeine-administration protocol.
  
  
  RESULTS
  This did not alter the threshold for the induction of seizures by a subconvulsant dose of pilocarpine (200 mg/kg, i.p.) or kainic acid (8 mg/kg, i.p.). Similarly, challenging another group of animals with the same doses of pilocarpine or kainate 12 h after the withdrawal of the same caffeine-administration protocol did not lead to any significant changes in seizures.
  
  
  CONCLUSIONS
  With the pilocarpine model of epilepsy, we were not able to find any significant difference in seizure profile that could stem from either caffeine administration or its withdrawal. Despite the extensive laboratory evidence on the convulsant properties of xanthine derivatives in animal models of epilepsy, such strong evidence is lacking in clinical settings. Our current findings with the administration of caffeine at doses similar to those of daily life both support and confirm the clinical experience.
authors.affiliation: Department of Physiology, UNIFESP, São Paulo, Brazil.
authors.forename: Marcelo Q
authors.initials: MQ
authors.lastname: Hoexter
authors.forename: Pedro S
authors.initials: PS
authors.lastname: Rosa
authors.forename: Sergio
authors.initials: S
authors.lastname: Tufik
authors.forename: Luiz E
authors.initials: LE
authors.lastname: Mello
mesh_terms: D000241:Adenosine / Q000097:blood / Q000502:physiology; D000818:Animals; D002110:Caffeine / Q000009:adverse effects* / Q000494:pharmacology*; D040503:Coffea / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000502:physiology; D004833:Epilepsy, Temporal Lobe / Q000139:chemically induced / Q000503:physiopathology; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D010862:Pilocarpine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology*; D013226:Status Epilepticus / Q000139:chemically induced* / Q000503:physiopathology*; D013375:Substance Withdrawal Syndrome / Q000097:blood / Q000209:etiology* / Q000503:physiopathology
chemical_list: D010862:Pilocarpine; D002110:Caffeine; D000241:Adenosine; D007608:Kainic Acid