J. Filakovszky et al., A serotonin-1A receptor agonist and an N-methyl-D-aspartate receptor antagonist oppose each others effects in a genetic rat epilepsy model, NEUROSCI L, 261(1-2), 1999, pp. 89-92
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.