Effects of an adenosine analogue administration on the striatal NMDA receptors in an experimental model of epilepsy

Specific [H-3]-MK801 binding to rat NMDA receptors following the administra tion of the convulsant drug 3-mercaptopropionic acid (MP) and the adenosine analogue cyclopentyladenosine (CPA) was studied in striatal membrane fract ions. MP administration (150 mg/kg, i.p.) caused an increase of 53% and 52% in [H-3]-MK801 binding during seizure and the postseizure period respectiv ely. Administration of CPA (2 mg/kg, i.p.) raised [H-3]-MK801 binding by 72 %. When CPA was administered 30 min before MP and rats sacrificed at seizur e (CPA + MPc), an increase of 64%, was observed. Saturation results indicat e that receptor sites increased their maximal binding capacity (B-max) in a ll treatments while the apparent dissociation constant (K-d) remained uncha nged. MP administration brought about an increase of 52% and 42% in [H-3]-M K801 binding sites during seizure and postseizure respectively. Administrat ion of CPA raised receptor density by 75%. When CPA was administered 30 min before MP and rats sacrificed at seizure (CPA + MPc), an increase of 62%, was observed. These results show that striatal NMDA receptors have a select ive role in seizure activity in the basal ganglia and that the adenosine an alogue administration may modify [H-3]-MK801 binding in a way similar to th at of the convulsant drug. (C) 2000 Elsevier Science Ltd. All rights reserv ed.