EFFECTS OF N-6-CYCLOPENTYL ADENOSINE AND 8-CYCLOPENTYL-1,3-DIPROPYLXANTHINE ON N-METHYL-D-ASPARTATE INDUCED SEIZURES IN MICE

The effect of the adenosine A(1) receptor agonist N-6-cyclopentyladeno sine (CPA) and antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) on N-methyl-D-aspartate (NMDA)-evoked seizures was studied in C57BL/6 mic e (20/group). Animals were injected i.p. either with CPA (0.5, 1, 2 mg /kg) or CPX (1, 2 mg/kg) 15 min prior to administration of NMDA (30, 6 0, 125 mg/kg). Administration of NMDA alone resulted in a complete loc omotor arrest at 30 mg/kg, while clonic/tonic seizures and progressive ly increasing mortality were seen at higher doses. Prior administratio n of CPA resulted either in a delay of seizure onset and unchanged mor tality (0.5 mg/kg CPA, 60 mg/kg NMDA) or in elimination of tonic episo des and a significant reduction in postictal mortality (1, 2 mg/kg CPA ; 60, 125 mg/kg NMDA). Pretreatment with CPX at either 1 or 2 mg/kg el iminated locomotor depression in animals injected with NMDA at 30 mg/k g. At 60 mg/kg NMDA, the effect of CPX administration resulted in mort ality equivalent to that seen with 125 mg/kg NMDA administered alone. The results indicate that A(1) receptor agonists may protect against N MDA-evoked seizures and that the adenosine A(1) receptor may be direct ly involved in these actions.