A serotonin-1A receptor agonist and an N-methyl-D-aspartate receptor antagonist oppose each others effects in a genetic rat epilepsy model

The WAG/RIJ rats exhibit spontaneously occurring spike-wave discharges (SWD ) accompanied by behavioural phenomena, with characteristics similar to the human absence type epilepsy. To study the mechanisms involved in this type of epileptiform activity we investigated the effects of the serotonin-1A ( 5-HT1A) receptor agonist 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT ) and the N-methyl-D-aspartate (NMDA) receptor antagonist (+)-5-methyl-10,1 1-dihydro-5H-dibenno [a,d]cyclohepten-5,10-imine maleate (MK-801). Intracer ebroventricular (i.c.v.) injection of 8-OH-DPAT caused marked, dose depende nt increase, MK-801 a decrease in the cumulative duration and number of spi ke-wave discharges. Pretreatment with MK-801 (10 mu g/rat i.c.v.) abolished the increase caused by 8-OH-DPAT (20 mu g/rat i.c.v.), but the decrease in SWD to MK-801 was counterbalanced by 8-OH-DPAT. These data provide evidenc e for an interaction of glutamatergic and serotonergic mechanisms in the tr iggering and maintenance of epileptic activity in this genetic model of abs ence epilepsy. (C) 1999 Published by Elsevier Science Ireland Ltd. All righ ts reserved.