neurons and activate CB1R expressed on astrocytes. The astrocytes respond with an increase in calcium from intracellular stores leading to the release of gliotransmitters (Figure 1B), capable of modulating the presynaptic and postsynaptic circuit elements [47,50,51]. Through these mechanisms eCBs can inhibit pre-synaptic neurotransmitter release at both GABA and glutamate terminals, thus modulating several neurotransmitter systems [5,47,52]. As illustrated for dopamine neurons, CB1 receptors expressed at presynaptic glutamatergic and GABAergic inputs to DA neurons may facilitate or suppress dopaminergic neuronal activity by modifying such inputs [53,54,55]. CB1 receptors on GABAergic terminals (Figure 2A) can facilitate dopaminergic activity through suppression of the inhibitory input onto GABA receptors present on DA neurons [56,57,58,59], leading to an increase of DA release in areas such as the nucleus accumbens (NAc) of the ventral striatum.
