Review Article

Antiaversive Effects of Cannabinoids: Is the Periaqueductal Gray Involved?

Figure 1

Possible effects of cannabinoids in the dlPAG. Glutamatergic inputs from forebrain structures such as the dorsomedial part of the ventromedial hypothalamic nucleus (dmVMH) and dorsal premammilary hypothalamic nucleus (PmD) activate a local neural substrate that mediates defensive responses [88]. This substrate is under GABAergic and serotonergic inhibitory influence [26]. Activation of CB1 receptors by cannabinoids such as AEA interferes with presynaptic glutamate (Glu) and GABA (Ga) neurotransmitter release. CB1-mediated decrease of glutamate release would promote anxiolytic-like effects. Activation of TRPV1 presynaptic receptors, on the other hand, would produce opposite effects. The anxiolytic effects of cannabidiol (CBD), a nonpsychotomimetic cannabinoid, in the dlPAG are not mediated by CB1 receptors, but probably involve activation of postsynaptic 5HT1A receptors. The bell-shaped dose-response curves observed with AEA and CBD may depend on activation of TRPV1 receptors. Regarding AEA, a presynaptic decrease of GABA release could also be related to this effect.
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