Activation of the CB1 cannabinoid receptor protects cultured mouse spinal neurons against excitotoxicity

Significant advances are being made towards understanding the genetic basis for spinal neurodegenerative diseases, however, effective pharmacotherapy remains elusive. One of the primary theories underlying neuron vulnerabilit y is susceptibility to excitotoxicity. We present for the first time eviden ce that the activation of the CB1 cannabinoid receptor effectively modulate s kainate toxicity in primary neuronal cultures prepared from mouse spinal cord. Addition of Delta (9)-tetrahydrocannabinol to the culture medium atte nuated the toxicity produced by kainate. The CB1 receptors were localized t o spinal neurons and astrocytes. The neuroprotective effect was blocked wit h the CB1 receptor antagonist, SR141716A, indicating a receptor-mediated ef fect (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.