N-METHYL-D-ASPARTATE RECEPTORS MEDIATE ACTIVATION OF THE C-FOS PROTOONCOGENE IN A MODEL OF BRAIN INJURY

The proto-oncogene c-fos is rapidly and transiently induced in the CNS by a variety of stimuli. Brain injury, disruption of pia-arachnoid in a limited area, is one of the situations that leads to a dramatic increase in c-fos immunoreactivity. This increase is limited to the lesioned hemisphere. Injections of atropine (25 mg/kg, i.p.), naltrexone (5 mg/kg, i.p.), nifedipine (5 mg/kg, i.p.), and f N-(6-aminohexyl-5-chloro-1-naphthalenesulfonamide (20 mg/kg, i.p.), prior to the injury, did not affect the activation of c-fos as assessed by immunohistochemistry in adult Sprague-Dawley rats perfused 2 h after the lesion. The non-competitive N-methyl-d-aspartate antagonists ketamine (100 mg/kg, i.p.) and MK-801 {(+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate} (1 and 3 mg/kg, i.p.) markedly reduced c-fos activation. Phencyclicline (10 mg/kg, i.p.) produced a slight reduction in damage-induced fos activation. This study suggests that c-fos activation in this particular model isN-methyl-d-aspartate receptor mediated and supports the idea that the fos proto-oncogene might play a role in plasticity and/or neurotoxic changes following brain damage. © 1990.