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Endocannabinoid Receptors: CNS Localization of the CB1 Cannabinoid Receptor

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Behavioral Neurobiology of the Endocannabinoid System

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 1))

Abstract

The evolution of plant metabolic pathways to invent compounds which distract predators, and the history of medicine to find treatments for diseases, often share a common logic. An attractive example to illustrate the rationale behind this is the Cannabis sativa plant, which was exploited for its widespread therapeutic effects for several thousand years, but historical “prescriptions” highlighted its distractive behavioral side-effects if abused. This chapter aims to explain the characteristically wide pharmacological and behavioral profile of the Cannabis plant by pointing to the ubiquitous anatomical distribution of CB1 cannabinoid receptors, its predominant molecular target, throughout the nervous system. However, in contrast to their abundant regional and cellular localization, the subcellular arrangement of CB1 receptors and the enzymes involved in the metabolism of its main endogenous ligand, 2-arachidonoylglycerol (2-AG), are strikingly polarized on the neuronal surface in the adult brain. Though there are still several unresolved issues, the known pieces of the puzzle outline a picture in which the biosynthetic machinery for 2-AG is accumulated in the somatodendritic compartment of neurons, whereas its receptor and degrading enzyme are both found on axon terminals. This molecular architecture suggests that a main physiological role of endocannabinoid signaling is the retrograde regulation of synaptic transmission, and the present chapter aims to summarize compelling evidence that it is an ancient and fundamental component of several distinct types of synapses throughout the nervous system.

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Abbreviations

2-AG:

2-Arachidonoylglycerol

DGL:

Diacylglycerol lipase

FAAH:

Fatty acid amide hydrolase

MGL:

Monoacylglycerol lipase

NAE:

N-Acylethanolamine

RER:

Rough endoplasmic reticulum

VGCC:

Voltage-gated calcium channels

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Acknowledgements

This work was supported by ETT 561/2006 and by the János Bolyai scholarship. The author is very grateful to Drs. Tamás F. Freund, Norbert Hájos, Ken Mackie, Daniele Piomelli and Masahiko Watanabe for their long-term collaborative support of his work on the endocannabinoid system. The author is also indebted to Ms. Anikó Ludányi, Rita Nyilas, Gabriella Urbán and Mr. Barna Dudok for their help with the preparation of figures and to Drs. Miles Herkenham, Jarmo Laitinen and Masahiko Watanabe for their kind contribution of figures to this book chapter.

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  1. Institute of Experimental Medicine, Hungarian Academy of Sciences, H-1083, Budapest, Szigony utca 43, Hungary

    István Katona

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Correspondence to István Katona .

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  1. Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, United Kingdom

    Dave Kendall

  2. Queen's Medical Centre, University of Nottingham, Nottingham, NG7 2UH, United Kingdom

    Stephen Alexander

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Katona, I. (2009). Endocannabinoid Receptors: CNS Localization of the CB1 Cannabinoid Receptor. In: Kendall, D., Alexander, S. (eds) Behavioral Neurobiology of the Endocannabinoid System. Current Topics in Behavioral Neurosciences, vol 1. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-88955-7_3

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