REPEATED TREATMENT WITH ADENOSINE A(1) RECEPTOR AGONIST AND ANTAGONIST MODIFIES THE ANTICONVULSANT PROPERTIES OF CPPENE

The effects of repeated administration of the selective adenosine A(1) receptor agonist 2-chloro-N-6-cyclopentyladenosine (CCPA), the select ive adenosine A(2) receptor agonist 2-hexynyl-5'-N-ethylcarboxamidoade nosine (2HE-NECA), the non-selective adenosine A(1)/A(2) receptor agon ist 5'-N-ethylcarboxamidoadenosine (NECA), the selective adenosine A(1 ) receptor antagonist 8-cyclopentyl-1,3 dipropylxanthine (DPCPX) and t he selective adenosine A(2) receptor antagonist l)-pyrazolo-(4,3-e)1,2 ,4-triazolo(1,5-c)pyrimidine (SCH 58261) on the anticonvulsant activit y of 3-(2-carboxypiperazine-4y)propenyl-1-phosphonic acid (CPPene), a selective N-methyl-D-aspartate receptor antagonist, were evaluated in audiogenic sensible dilute brown agouti mice DBA/2J (DBA/2). Mice were treated intraperitoneally twice daily for 7 days with CCPA 0.11 mg/kg , 2HE-NECA 0.056 mg/kg, NECA 0.11 mg/kg, DPCPX 0.5 mg/kg and SCH 58261 0.5 mg/kg followed by 2 vehicle injections (the wash-out period of 1 day) and subsequently CPPene was administered intracerebroventricularl y. Audiogenic seizures were delivered 30 min after CPPene administrati on. Repeated treatment with CCPA significantly reduced the anticonvuls ant properties of CPPene against audiogenic seizures. A weak and not s ignificant reduction of anticonvulsant effects of CPPene was observed following repeated administration of NECA, whilst the repeated adminis tration of 2HE-NECA did not decrease the antiseizure activity of CPPen e. Conversely, repeated administration of DPCPX markedly potentiated t he anticonvulsant properties of CPPene, whilst the repeated treatment with SCH 58261 did not increase the anticonvulsant activity of CPPene. The present results indicate that repeated treatment with CPPA, a sel ective adenosine A(1) receptor agonist, decreases the anticonvulsant p roperties of CPPene, whilst the repeated administration of DPCPX, a se lective adenosine A(1) receptor antagonist, potentiates the anticonvul sant effects of CPPene. The compounds acting as selective agonists or antagonists of adenosine A(2) receptors do not affect the antiseizure activity of CPPene. In conclusion, the repeated interaction of agonist s or antagonists with adenosine A(1) receptors seems to induce changes on anticonvulsant activity of CPPene, whereas drugs acting at adenosi ne A(2) receptors do not.