Tocris Bioscience Scientific Review Series

Two types of cannabinoid receptor have so far been identified.1,2 These are the CB1 receptor, cloned in 1990,3 and the CB2 receptor, cloned in 1993,4 both of which are members of the superfamily of G-protein-coupled receptors. The cloning of these receptors prompted the development of mice from which cannabinoid CB1 and/or CB2 receptors have been genetically deleted and these transgenic animals, particularly CB1 knockout mice, are now widely used to explore the physiological and pathological functions of cannabinoid receptors.1,5,6 CB1 receptors are found mainly at the terminals of central and peripheral neurons where they usually mediate inhibition of neurotransmitter release. They are also present in some non-neuronal cells, including immune cells. CB2 receptors are located predominantly in immune cells both within and outside the central nervous system, the functions of these receptors including modulation of cytokine release and of immune cell migration. In the brain, CB2 receptors are expressed by microglia,7 by blood vessels,7 and by some neurons.8,9 However, the role of neuronal CB2 receptors is currently unknown. The central distribution pattern of CB1 receptors is heterogeneous and accounts for several prominent pharmacological properties of CB1 receptor agonists, for example their ability to impair cognition and memory and to alter the control of motor function. Thus the cerebral cortex, hippocampus, lateral caudateputamen, substantia nigra pars reticulata, globus pallidus, entopeduncular nucleus and the molecular