A second endogenous cannabinoid that modulates long-term potentiation

  title={A second endogenous cannabinoid that modulates long-term potentiation},
  author={Nephi Stella and Paul Schweitzer and Daniele Piomelli},
Cannabinoid receptors are molecular targets for marijuana and hashish, the widespread drugs of abuse. These receptors are expressed in areas of the central nervous system that contribute in important ways to the control of memory, cognition, movement and pain perception. Indeed, such functions can be strongly influenced by cannabinoid drugs, with consequences that include euphoria, analgesia, sedation and memory impairment. Although the pharmacology of cannabinoid drugs is now beginning to be… 

Cannabinoid modulation of neuronal activity in adult rat hippocampus.

A second endogenous cannabinoid ligand, 2-arachidonylglycerol (2-AG), is found in brain and the levels of 2-AG markedly increase upon fiber tract stimulation in hippocampal slices, suggesting that 2- AG may act as a signaling molecule in hippocampus.

Cannabis and the brain.

  • L. Iversen
  • Biology, Psychology
    Brain : a journal of neurology
  • 2003
Central effects of cannabinoids include disruption of psychomotor behaviour, short-term memory impairment, intoxication, stimulation of appetite, antinociceptive actions (particularly against pain of neuropathic origin) and anti-emetic effects.

The neurobiology and evolution of cannabinoid signalling.

  • M. ElphickM. Egertová
  • Biology
    Philosophical transactions of the Royal Society of London. Series B, Biological sciences
  • 2001
A model of cannabinoid signalling is presented in which anandamide is synthesized by postsynaptic cells and acts as a retrograde messenger molecule to modulate neurotransmitter release from presynaptic terminals, concluding that the cannabinoid signalling system may be quite restricted in its phylogenetic distribution.

Mechanism of Cannabinoid Effects on Long-Term Potentiation and Depression in Hippocampal CA1 Neurons

The results indicate that cannabinoid receptor activation does not directly inhibit the molecular mechanisms responsible for long-term synaptic plasticity but instead impairs LTP and LTD by reducing presynaptic neurotransmitter release to a level below that required to depolarize the postsynaptic membrane to relieve Mg2+ blockade of NMDA receptors.

The effects of cannabinoids on the brain

  • A. Ameri
  • Biology
    Progress in Neurobiology
  • 1999

Cardiovascular actions of cannabinoids and their generation during shock

Recent studies indicate that a peripheral endogenous cannabinoid system in circulating macrophages and platelets is activated in hemorrhagic and septic shock and may contribute to the hypotension associated with these conditions via activation of vascular cannabinoid receptors.

Cannabinoid disruption of learning mechanisms involved in reward processing

Roles for endogenous cannabinoids in shaping synaptic activity in cortical and subcortical brain circuits are examined, and mechanisms in which exogenous cannabinoids, such as Δ9-THC, interact with endocannabinoid systems to disrupt neuronal network oscillations are discussed.

Control of pain initiation by endogenous cannabinoids

It is shown that anandamide attenuates the pain behaviour produced by chemical damage to cutaneous tissue by interacting with CB1-like cannabinoid receptors located outside the CNS, and that locally generated an andamide and PEA may mediate this effect.


It is indicated that the CB1 receptor agonist increases the dopamine release from the depolarized synaptosomes through interaction with CB1 receptors, and the results suggest the involvement of an endogenous cannabinoid system in the regulation of dopamineRelease from synaptic terminals.



The endogenous cannabinoid receptor agonist anandamide impairs memory in rats

This is the first report that anandamide impairs memory; results suggest that endogenous cannabinoids may be involved in cognitive processes influencing memory.

Formation and inactivation of endogenous cannabinoid anandamide in central neurons

It is reported that anandamide is produced in and released from cultured brain neurons in a calcium ion-dependent manner when the neurons are stimulated with membrane-depolarizing agents, indicating that multiple biochemical pathways may participate in an andamide formation in brain tissue.

The pharmacological activity of anandamide, a putative endogenous cannabinoid, in mice.

It is demonstrated that anandamide produces effects in a tetrad of tests used to predict cannabimimetic activity and supports the contention of its role as an endogenous cannabinoid ligand.

Pharmacology of cannabinoid receptors.

  • A. Howlett
  • Biology, Chemistry
    Annual review of pharmacology and toxicology
  • 1995
Two subtypes of cannabinoid receptors, CB1 and CB2, have been described to date, although future investigations may elucidate other receptors, and three classes of agonist ligands regulate cannabinoid receptors: cannabinoid, aminoalkyl-indole, and eicosanoid derivatives.

Cannabinoid receptor localization in brain.

  • M. HerkenhamA. Lynn K. Rice
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 1990
The potencies of a series of natural and synthetic cannabinoids as competitors of [3H]CP 55,940 binding correlated closely with their relative potencies in several biological assays, suggesting that the receptor characterized in the in vitro assay is the same receptor that mediates behavioral and pharmacological effects of cannabinoids, including human subjective experience.

2-Arachidonoylglycerol: a possible endogenous cannabinoid receptor ligand in brain.

2-Arachidonoylglycerol was shown to bind appreciably to the cannabinoid receptor in competitive inhibition experiments and may be an endogenous cannabinoid receptor ligand in the brain.

Isolation and structure of a brain constituent that binds to the cannabinoid receptor.

Arachidonylethanolamide, an arachidonic acid derivative in porcine brain, was identified in a screen for endogenous ligands for the cannabinoid receptor. The structure of this compound, which has

Biosynthesis of an Endogenous Cannabinoid Precursor in Neurons and its Control by Calcium and cAMP

The results thus indicate that NAPE levels in cortical neurons are controlled by Ca2+ ions and cAMP, and regulatory effect may participate in maintaining a supply of cannabimimetic N-acylethanolamines during synaptic activity, and prime target neurons for release of these bioactive lipids.

Characterization of CB1 Receptors on Rat Neuronal Cell Cultures: Binding and Functional Studies Using the Selective Receptor Antagonist SR 141716A

Results show nanomolar efficiencies for CP 55940 and WIN 55212‐2 on adenylyl cyclase activity and no effect on any other signal transduction pathway investigated in primary neuronal cultures.