Endocannabinoids contribute to short-term but not long-term mGluR-induced depression in the hippocampus.
Activation of postsynaptic group 1 metabotropic glutamate receptors (mGluRs) by the agonist DHPG causes a long-term depression (DHPG-LTD) of excitatory transmission in the CA1 region of the hippocampus, as well as causing the release of endocannabinoids from pyramidal cells. As cannabinoid agonists cause a presynaptic inhibition at these synapses and DHPG-LTD is thought to be expressed, at least in part, by a presynaptic mechanism, we examined the possibility that endocannabinoids mediated DHPG-LTD. We find that antagonists of cannabinoid receptors reduce the acute depression induced by DHPG, but have no effect on the lasting depression. Furthermore, both the acute and the lasting effects of DHPG were unaffected in the CB1 knockout mouse. These findings suggest that endocannabinoids, acting on a non-CB1 cannabinoid receptor, contribute to the acute depression but not to DHPG-LTD. Presumably some other retrograde signalling mechanism is responsible for DHPG-LTD.
Rouach
Nathalie
N
Departments of Cellular and Molecular Pharmacology and Physiology, University of California-San Francisco, Genentech Hall, 600 16th Street, Box 2140, San Francisco, CA 94143, USA.
Nicoll
Roger A
RA
D000818:Animals; D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005231:Fatty Acids, Unsaturated / Q000819:agonists / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D036881:Long-Term Synaptic Depression / Q000502:physiology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D009435:Synaptic Transmission / Q000502:physiology
D063385:Cannabinoid Receptor Modulators; D063388:Endocannabinoids; D005231:Fatty Acids, Unsaturated; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D018094:Receptors, Metabotropic Glutamate; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol