ACUTE EFFECTS OF IRRADIATION ON THE RAT-BRAIN - PROTECTION BY GLUTAMATE BLOCKADE

Riluzole (2-amino-6-trifluorothethoxy benzothiazole), dizocilpine (MK- 801; ,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine maleate), and lamotrigine (3,5-diamino-6-(2,3-dichlorophenyl)-1,2-triazine), agents reported to have neuroprotective actions, and WR2721 (S-2-(3-aminoprop ylamino)-ethylphosphorothioic acid), a radioprotector, were evaluated in 15-day-old rats that underwent a 2.5 Gray (Gy) irradiation from a c obalt 60 source. 20 min after irradiation, riluzole (0.5-8 mg/kg), diz ocilpine (0.1-1 mg/kg), lamotrigine (25 mg/kg), WR 2721 (75 mg/kg) or vehicle, were injected intraperitoneally. 6 h after irradiation, behav ioural and histological evaluations revealed that exposure to 2.5 Gy c aused hypolocomotion, stumbling gait and somnolence, which was signifi cantly reduced, from the dose of 4 mg/kg i.p. of riluzole. A dose-depe ndent protection of neurones in the dentate gyrus, starting from the d ose of 1 mg/kg i.p. was also seen. Dizocilpine caused behavioural modi fications but significantly reduced neuronal damage. Lamotrigine signi ficantly increased neuronal damage while WR 2721 conferred no protecti on. In conclusion, two blockers of glutamatergic neurotransmission con ferred significant protection against brain damage caused by ionizing irradiation when administered subsequent to exposure.