Neuroprotective effect of eliprodil: attenuation of a conditioned freezing deficit induced by traumatic injury of the right parietal cortex in the rat.
We have previously demonstrated that a lateral fluid percussion-induced traumatic lesion of the right parietal cortex can lead to a deficit in a conditioned freezing response and that this deficit can be attenuated by both pre- and postlesion administration of the NMDA receptor antagonist dizocilpine. In the present study, we investigated the effects of eliprodil, a noncompetitive NMDA receptor antagonist acting at the polyamine modulatory site, which also acts as a Ca2+ channel blocker, on the trauma-induced conditioned freezing deficit. Eliprodil produced a 50% reduction in this deficit when administered as three 1 mg/kg injections i.v. at 15 min, 6 h, and 24 h following the lesion. Approximately the same degree of protection was afforded when 2 x 1.5 mg/kg were administered 6 and 24 h and equally at 12 and 24 h after surgery (56% and 59%, respectively). A single treatment (3 mg/kg) at 24 h was ineffective against the deficit. The protection afforded with treatment at 6 and 24 h after lesion was dose dependent, with a minimal active dose of 2 x 0.75 mg/kg. These data complement those previously published on the ability of eliprodil to reduce lesion volume following traumatic brain injury and show, in addition, that the neuroprotective effect has functional consequences.
Hogg
S
S
Synthélabo Recherche, Rueil-Malmaison, France.
Perron
C
C
Barnéoud
P
P
Sanger
D J
DJ
Moser
P C
PC
D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy*; D003072:Cognition Disorders / Q000209:etiology / Q000517:prevention & control*; D003214:Conditioning, Classical / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005239:Fear / Q000502:physiology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010296:Parietal Lobe / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D013996:Time and Motion Studies
D018696:Neuroprotective Agents; D010880:Piperidines; C058083:eliprodil