Anatomical Distribution of Receptors, Ligands and Enzymes in the Brain and in the Spinal Cord: Circuitries and Neurochemistry

The endocannabinoid system has emerged during the last two decades as a very important regulator of neuronal and cellular activity in many different body tissues and particularly in the central and peripheral nervous systems. The endocannabinoid system constitutes of lipid signaling molecules (the endocannabinoids), the enzymatic machineries for their synthesis and degradation, and their cellular targets, the cannabinoid receptors. “Bona fide” targets of endocannabinoids are the G protein-coupled cannabinoid receptors type 1 and type 2 (CB₁ and CB₂ receptors, respectively). However, recent evidence indicates that endocannabinoids also have other targets besides “classical” cannabinoid receptors. Furthermore, the steadily growing list of newly discovered elements of endocannabinoid signaling further expands the definition of the endocannabinoid system on an almost daily base. In this chapter, we will describe the anatomical distribution of the various elements of the endocannabinoid system in the brain, the spinal cord and the peripheral nervous system. In particular, we will address the distribution of receptors (CB₁ and CB₂ receptors and other targets of endocannabinoids), of enzymes involved in the synthesis and degradation of endocannabinoids, and of the two major endocannabinoids described so far, anandamide and 2-arachidonoyl-glycerol. Particular emphasis will be given to new findings indicating a larger distribution of the endocannabinoid system in nervous tissues than previously believed. The need for improvement of unbiased techniques for the detection of various elements of the endocannabinoid system will be also underlined, which will allow a more precise identification of the sites where endocannabinoid signalling exerts important physiological and pathophysiological functions.