CB1 cannabinoid receptors and on-demand defense against excitotoxicity.
1. Science. 2003 Oct 3;302(5642):84-8.
CB1 cannabinoid receptors and on-demand defense against excitotoxicity.
Marsicano G(1), Goodenough S, Monory K, Hermann H, Eder M, Cannich A, Azad SC,
Cascio MG, Gutiérrez SO, van der Stelt M, López-Rodriguez ML, Casanova E, Schütz
G, Zieglgänsberger W, Di Marzo V, Behl C, Lutz B.
Author information:
(1)Molecular Genetics of Behaviour, Max-Planck-Institute of Psychiatry,
Kraepelinstrabetae 2-10, 80804 Munich, Germany.
Comment in
Science. 2003 Oct 3;302(5642):65-7.
Abnormally high spiking activity can damage neurons. Signaling systems to protect
neurons from the consequences of abnormal discharge activity have been
postulated. We generated conditional mutant mice that lack expression of the
cannabinoid receptor type 1 in principal forebrain neurons but not in adjacent
inhibitory interneurons. In mutant mice,the excitotoxin kainic acid (KA) induced
excessive seizures in vivo. The threshold to KA-induced neuronal excitation in
vitro was severely reduced in hippocampal pyramidal neurons of mutants. KA
administration rapidly raised hippocampal levels of anandamide and induced
protective mechanisms in wild-type principal hippocampal neurons. These
protective mechanisms could not be triggered in mutant mice. The endogenous
cannabinoid system thus provides on-demand protection against acute
excitotoxicity in central nervous system neurons.
DOI: 10.1126/science.1088208
PMID: 14526074 [Indexed for MEDLINE]