356 B. Szabo and E. Schlicker
Fig. 8.Effects of cannabinoids on synaptic transmission. Activation of the CB 1 receptor at the presynaptic
axon terminal inhibits transmitter release from the synaptic vesicle. Three mechanisms can be involved in
presynaptic inhibition (Xrefers to unknown second messengers): inhibition of voltage-dependent calcium
channels, activation of potassium channels and direct interference with the vesicle release machinery. The CB 1
receptor can be activated by exogenous agonists, but also by the endocannabinoids anandamide (AEA)and
2-arachidonoylglycerol (2-AG), which are released from the postsynaptic neuron by passive and/or facilitated
diffusion. The synthesis of endocannabinoids is triggered by a depolarisation-induced (Vm,membrane
potential) calcium influx or by activation of Gq/11protein-coupled receptors
functional system? One functional role of CB 1 receptors is their participation
in retrograde signalling, at least with respect to fast excitatory and inhibitory
transmission. Endogenous cannabinoids released from postsynaptic neurons can
diffuse to presynaptic axon terminals where they produce presynaptic inhibition
(Ohno-Shosaku et al. 2001; Wilson and Nicoll 2001). The trigger for synthesis of en-
docannabinoids is depolarisation of postsynaptic neurons or activation of Gαq/11
protein-coupled receptors of postsynaptic neurons (see Fig. 8). This phenomenon
is called depolarisation-induced suppression of inhibition (DSI; if inhibitory neu-
rotransmission is suppressed by endocannabinoids) or depolarisation-induced
suppression of excitation (DSE; if excitatory neurotransmission is suppressed by
endocannabinoids). This new research field was reviewed by Wilson and Nicoll
(2002) and Freund et al. (2003) and is also reviewed in the chapter by Vaughan and
Christie (this volume).