8-OH-DPAT and MK-801 affect epileptic activity independently of vigilance.
Vigilance and parallel occurrence of epileptic activity after administration of the 5-HT(1A) agonist 8-OH-DPAT and the NMDA receptor antagonist MK-801 were studied in the genetic absence epilepsy model WAG/Rij rats. Spike-wave discharges (SWD) were present predominantly in passive awake and light slow wave sleep (SWS1) either in control animals or after treatments. Injection of 8-OH-DPAT (20.0 microg/rat i.c.v.) caused marked increase and MK-801 (10.0 microg/rat i.c.v.) decrease in SWD densities, thus the ratios of SWD in passive awake and in SWS1. SWD densities of MK-801 plus 8-OH-DPAT in combination were similar to those of CSF+CSF treated control rats. Both 8-OH-DPAT and MK-801 transiently increased the duration of active awake, increased latency and decreased duration of rapid eye movement (REM) sleep. 8-OH-DPAT increased the amount of SWD despite the decrease in the duration of SWS1. MK-801 decreased the amount of SWD despite the lack of significant change in duration of passive awake or SWS1. Pre-treatment with MK-801 reversed 8-OH-DPAT- induced increase in duration of SWD without any effect on 8-OH-DPAT-induced changes in sleep parameters. Our studies provide evidence that 8-OH-DPAT-induced epileptic activity is independent of its effect on sleep, and that interaction of serotonergic and glutamatergic systems plays a role in the generation of SWD, but not in the regulation of vigilance and sleep.
Filakovszky
J
J
Laboratory of Neurochemistry and Experimental Medicine, National Institute of Psychiatry and Neurology, Huvosvolgyi ut 116, 1021 Budapest, Hungary.
Kantor
S
S
Halasz
P
P
Bagdy
G
G
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001288:Attention / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004827:Epilepsy / Q000503:physiopathology*; D007276:Injections, Intraventricular; D008297:Male; D051381:Rats; D012890:Sleep / Q000187:drug effects
D016291:Dizocilpine Maleate; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin