Striatum adenosine A(2) receptors are modified during seizure: Effect of cyclopentyladenosine administration

Rat CNS adenosine A(2A) receptors were studied after administration of the convulsant drug 3-mercaptopropionic acid (MP) and the adenosine analogue cy clopentyladenosine (CPA) by means of a quantitative autoradiographic method . Specific binding was quantified in striatum only. The highest density was found in caudate-putamen (2.50 fmol/mm(2)), followed by nuclei accumbens ( 1.85 fmol/mm(2)) and the lowest values in the olfactory tubercle (1.26 fmol /mm(2)). These differerences were statiscally significant. MP administratio n (150 mg/kg) caused significant increases (12-18%) in caudate-putamen and nuclei accumbens in both stages: seizure and postseizure and no changes in the olfactory tubercle. CPA administration (2 mg/kg) originated a rise of 1 6% in nuclei accumbens but no change in the other two regions. When CPA was injected 30 minutes before MP, an increase (18 to 45%) in caudate-putamen and nuclei accumbens at seizure and postseizure stages was observed. Satura tion results, in striatal membrane fraction, indicate that receptor sites i ncreased their maximal binding capacity (Bmax) while the apparent dissociat ion constant (Kd) remained unchanged. These results suggest the involvement of the adenosine A(2A) receptors in convulsant activity and that CPA admin istration at the dose selected brings about a rise in neuronal excitability in this area.