Kainate-induced functional deficits are not blocked by MK-801.
Male, Fischer-344 rats were pretreated with MK-801 (0.1, 1.0 or 10.0 mg/kg, i.p.) prior to bilateral injection of kainate (0.33 micrograms/site) into the dorsal and ventral hippocampus. Kainate impaired the acquisition of a water maze acquisition task 4 weeks after surgery, an effect not attenuated by pretreatment with MK-801. However, higher doses (1.0 and 10.0 mg/kg) of MK-801 reduced the amount of kainate-induced granule cell and to some extent CA1 pyramidal cell damage in the hippocampus. Kainate-induced CA3/CA4 damage was not affected by MK-801 pretreatment. MK-801 (10 mg/kg) also reduced the amount of thalamic damage produced by kainate. These data support the conclusion that intrahippocampal kainate-induced destruction of CA3/CA4 pyramidal cells is mediated by non-N-methyl-D-aspartate (non-NMDA) receptors and that kainate-induced loss of these cells is associated with the neurobehavioral effects of intrahippocampally administered kainate.
Rogers
B C
BC
Curriculum in Toxicology, University of North Carolina, Chapel Hill 27514.
Tilson
H A
HA
D000818:Animals; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D007608:Kainic Acid / Q000633:toxicity*; D007858:Learning / Q000187:drug effects*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*
D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D016291:Dizocilpine Maleate; D007608:Kainic Acid