Abstract
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 vulnerability is susceptibility to excitotoxicity. We present for the first time evidence that the activation of the CB(1) cannabinoid receptor effectively modulates kainate toxicity in primary neuronal cultures prepared from mouse spinal cord. Addition of Delta(9)-tetrahydrocannabinol to the culture medium attenuated the toxicity produced by kainate. The CB(1) receptors were localized to spinal neurons and astrocytes. The neuroprotective effect was blocked with the CB(1) receptor antagonist, SR141716A, indicating a receptor-mediated effect.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Astrocytes / drug effects
-
Astrocytes / metabolism
-
Cells, Cultured
-
Dronabinol / pharmacology*
-
Embryo, Mammalian
-
Excitatory Amino Acid Agonists / toxicity*
-
Hallucinogens / pharmacology*
-
Kainic Acid / toxicity*
-
Mice
-
Neurons / drug effects
-
Neurons / metabolism
-
Neurotoxins / pharmacology
-
Piperidines / pharmacology
-
Pyrazoles / pharmacology
-
Receptors, Cannabinoid
-
Receptors, Drug / antagonists & inhibitors
-
Receptors, Drug / metabolism*
-
Rimonabant
-
Spinal Cord / drug effects*
-
Spinal Cord / metabolism*
Substances
-
Excitatory Amino Acid Agonists
-
Hallucinogens
-
Neurotoxins
-
Piperidines
-
Pyrazoles
-
Receptors, Cannabinoid
-
Receptors, Drug
-
Dronabinol
-
Rimonabant
-
Kainic Acid