Evidence for the involvement of the adenosine A(2A) receptor in the lowered susceptibility to pentylenetetrazol-induced seizures produced in mice by long-term treatment with caffeine.
Long-term caffeine intake has been reported to decrease the susceptibility to convulsants in mice. Occurrence of seizures following long-term oral administration of caffeine (0.3g/l) was investigated using adenosine A(2A) receptor knockout (A(2A)R KO) and control (A(2A)R WT) mice. Clonic seizures induced by acute pentylenetetrazol (PTZ, 50mg/kg i.p.) were significantly attenuated in adenosine A(2A)R KO mice drinking only water and reduced by a 14-day caffeine treatment in adenosine A(2A)R WT mice. In addition we showed a protecting effect of a 21-day caffeine treatment in A(2A)R WT mice against kindled seizures induced by PTZ in an increasing dose schedule. Summing up, these protective effects against PTZ-induced seizures occurring when adenosine A(2A)R is absent or chronically blocked by a relevant dose of caffeine may be related to a decreased neuronal excitability.
El Yacoubi
Malika
M
Unité de Neuropsychopharmacologie Expérimentale, F.R.E. 2735 C.N.R.S., I.F.R.M.P. 23, Faculté de Médecine et Pharmacie, 22 Boulevard Gambetta, 76183 Rouen Cedex, France.
Ledent
Catherine
C
Parmentier
Marc
M
Costentin
Jean
J
Vaugeois
Jean-Marie
JM
D000704:Analysis of Variance; D000818:Animals; D002110:Caffeine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010433:Pentylenetetrazole; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage*; D011930:Reaction Time / Q000187:drug effects / Q000235:genetics; D043705:Receptor, Adenosine A2A / Q000172:deficiency / Q000502:physiology*; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D013997:Time Factors
D010726:Phosphodiesterase Inhibitors; D043705:Receptor, Adenosine A2A; D002110:Caffeine; D010433:Pentylenetetrazole