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Neuroprotection by Δ9-Tetrahydrocannabinol, the main active compound in marijuana, against ouabain-induced in vivo excitotoxicity

By M van der Stelt, WB Veldhuis, PR Bär, GA Veldink, JFG Vliegenthart and K Klaas Nicolaij


Excitotoxicity is a paradigm used to explain the biochemical events in both acute neuronal damage and in slowly progressive, neurodegenerative diseases. Here, we show in a longitudinal magnetic resonance imaging study that ¿9-tetrahydrocannabinol (¿9-THC), the main active compound in marijuana, reduces neuronal injury in neonatal rats injected intracerebrally with the Na+/K+-ATPase inhibitor ouabain to elicit excitotoxicity. In the acute phase ¿9-THC reduced the volume of cytotoxic edema by 22%. After 7 d, 36% less neuronal damage was observed in treated rats compared with control animals. Coadministration of the CB1 cannabinoid receptor antagonist SR141716 prevented the neuroprotective actions of ¿9-THC, indicating that ¿9-THC afforded protection to neurons via the CB1 receptor. In ¿9-THC-treated rats the volume of astrogliotic tissue was 36% smaller. The CB1 receptor antagonist did not block this effect. These results provide evidence that the cannabinoid system can serve to protect the brain against neurodegeneration

Publisher: 'Society for Neuroscience'
Year: 2001
DOI identifier: 10.1523/jneurosci.21-17-06475.2001
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Provided by: Repository TU/e
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