HALOTHANE AND DIAZEPAM INHIBIT KETAMINE-INDUCED C-FOS EXPRESSION IN THE RAT CINGULATE CORTEX

Background: Ketamine, a noncompetitive N-methyl-D-aspartate antagonist , has psychotomimetic side effects. Recent studies have shown that non competitive N-methyl-D-aspartate antagonists cause morphologic damage to the cingulate and retrosplenial cortices and induce c-fos protein ( c-Fos) in the same regions. Although benzodiazepines are effective in preventing these side effects, the neural basis of the drug interactio ns has not been established. Methods: The effects of diazepam and halo thane on c-Fos expression induced by ketamine were studied. Diazepam ( 1 and 5 mg/kg) or vehicle were administered subcutaneously, followed 7 min later by 100 mg/kg ketamine given intraperitoneally. Halothane (1 .0 and 1.80%), was administered continuously from 10 min before ketami ne administration until brain fixation. Two hours after ketamine injec tion, rats were perfused and their brains fixed and extracted. Brain s ections were prepared in a cryostat and c-Fos expression was detected using immunohistochemical methods. Results: Ketamine induced c-Fos-lik e immunoreactivity in the cingulate and retrosplenial cortices, thalam us, and neocortex. Diazepam suppressed the ketamine-induced c-Fos-like immunoreactivity in the cingulate and retrosplenial cortices in a dos e-dependent manner, leaving the thalamus and neocortex less affected. Halothane suppressed the ketamine-induced c-Fos-Like immunoreactivity in the cingulate and retrosplenial cortices and the neocortex in a dos e-dependent manner, leaving the thalamus relatively unaffected. Conclu sion: Halothane and diazepam inhibited ketamine induced c-Fos expressi on in the cingulate and retrosplenial cortices, leaving the thalamus r elatively unaffected.