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

Malika El Yacoubi (1) , Catherine Ledent (2) , Marc Parmentier (2) , Jean Costentin (1) , Jean-Marie Vaugeois (1)

1 Neuropsycho-pharmacologie expérimentale
2 ULB - Université libre de Bruxelles

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.

Mots clés: Seizure; Pentylenetetrazol; Kindling; Adenosine A2A receptor; Knockout mice; Caffeine

Domaines: Médecine humaine et pathologie

Malika El Yacoubi, Catherine Ledent, Marc Parmentier, Jean Costentin, Jean-Marie Vaugeois. 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. Neuropharmacology, 2008, 55 (1), pp.35-40. ⟨10.1016/j.neuropharm.2008.04.007⟩. ⟨hal-02185485⟩