Abstract
This report describes the effect of the dissociative anaesthetic ketamine, a non-competitive antagonist of the N-methyl-d-aspartate (NMDA) receptor, on the infectivity of the neurotropic rabies virus, in neuronal culture systems and in vivo. Ketamine (1–2 mm) produced an approximate 100–1000-fold decrease in the production of rabies virus in neuronal cell cultures. Rabies virus infection was also inhibited in non-neuronal cell lines (Baby Hamster Kidney fibroblasts) but the inhibitory effects appeared better expressed in cells of neuronal origin (neuroblastoma and primary neuronal cultures). The kainate/quisqualate competitive antagonist CNQX did not modify the course of rabies virus infection and modulators of known NMDA regulatory sites (Mg2+, Zn2+, HA-966) failed to antagonize the ketamine-mediated inhibition of rabies virus production in neuroblastoma cells. Furthermore, Ca2+-mobilization does not appear to be involved because Ca2+-depleted and EGTA-treated medium did not affect the normal production of rabies virus. The action of ketamine on rabies virus infection in vivo was also investigated; peripheral treatment of rats with this drug inhibited rabies virus infection in the thalamus, cortex and hippocampal formation (in particular the pyramidal layer of the CA1 region). Taken together, these data suggest that the ketamine-mediated inhibition of rabies virus production in vitro, although highly selective, is not acting via classic NMDA receptor-mediated mechanisms. However, the ketamine-mediated retardation of rabies virus infection in vivo may offer new prospects for post-exposure rabies antiviral therapy.
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