CRIP1a switches cannabinoid receptor agonist/antagonist-mediated protection from glutamate excitotoxicity

A shared pathology among many neurological and neurodegenerative disorders is neuronal loss. Cannabinoids have been shown to be neuroprotective in multiple systems. However, both agonists and antagonists of the CB(1) cannabinoid receptor are neuroprotective, but the mechanisms responsible for these actions remain unclear. Recently a CB(1) receptor interacting protein, CRIP1a, was identified and found to alter CB(1) activity. Here we show that in an assay of glutamate neurotoxicity in primary neuronal cortical cultures CRIP1a disrupts agonist-induced neuroprotection and confers antagonist-induced neuroprotection.