Endocannabinoids contribute to short-term but not long-term mGluR-induced depression in the hippocampus

Nathalie Rouach; Roger A Nicoll

doi:10.1046/j.1460-9568.2003.02823.x

Endocannabinoids contribute to short-term but not long-term mGluR-induced depression in the hippocampus

Eur J Neurosci. 2003 Aug;18(4):1017-20. doi: 10.1046/j.1460-9568.2003.02823.x.

Authors

Nathalie Rouach¹, Roger A Nicoll

Affiliation

¹ 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.

PMID: 12925027
DOI: 10.1046/j.1460-9568.2003.02823.x

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Cannabinoid Receptor Modulators
Endocannabinoids
Excitatory Postsynaptic Potentials / drug effects
Excitatory Postsynaptic Potentials / physiology
Fatty Acids, Unsaturated / agonists
Fatty Acids, Unsaturated / metabolism*
Hippocampus / drug effects
Hippocampus / physiology*
Long-Term Synaptic Depression / physiology*
Male
Methoxyhydroxyphenylglycol / analogs & derivatives*
Methoxyhydroxyphenylglycol / pharmacology
Mice
Mice, Knockout
Neural Inhibition / drug effects
Neural Inhibition / physiology*
Organ Culture Techniques
Patch-Clamp Techniques
Receptors, Cannabinoid
Receptors, Drug / antagonists & inhibitors
Receptors, Drug / genetics
Receptors, Drug / metabolism
Receptors, Metabotropic Glutamate / agonists
Receptors, Metabotropic Glutamate / antagonists & inhibitors
Receptors, Metabotropic Glutamate / metabolism*
Signal Transduction / physiology
Synaptic Transmission / physiology

Substances

Cannabinoid Receptor Modulators
Endocannabinoids
Fatty Acids, Unsaturated
Receptors, Cannabinoid
Receptors, Drug
Receptors, Metabotropic Glutamate
Methoxyhydroxyphenylglycol
3,4-dihydroxyphenylglycol