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Table 2: Effects of Cannabinoid-related drugs injected into the PAG of rats submitted to animal models of anxiety-related behaviors. (AEA: anandamide; ACEA: arachidonyl-2-chloro-ethylamide; CBD: cannabidiol; EPM: elevated plus-maze; VCT: Vogel conflict test; CFC: contextual fear conditioning; dlPAG: dorsolateral PAG; dPAG: dorsal (dorsolateral + dorsomedial) PAG; dmPAG: dorsomedial PAG; unpub: unpublished data.)

Drug PAG column Test Doses tested Effect (effective dose) Ref. Phytocannabinoids CBD dlPAG EPM, VCT 15–60 nmol Anxiolytic (30 nmol*) [86] Endocannabinoids AEA dlPAG EPM 0.05–50 pmol Anxiolytic (5 pmol*,1) [71] VCT 5 pmol Anxiolytic [73] CFC 5 pmol Anxiolytic [78] CB1 receptor agonists ACEA dlPAG EPM 0.05–5 pmol Anxiolytic (0.05 pmol*) [71] HU210 dPAG dPAG chemical stimulation 0.1–5g Attenuated flight responses (0.1–5g) [36] HU210 dmPAG Ultrasound-induced hyperlocomotion and freezing 5g Decreased hyperlocomotion, but increased freezing** [70] CB1 receptor antagonist AM251 dlPAG EPM, VCT, CFC 1–300 pmol No effect by itself, but blocked AEA and AM404 anxiolytic effects [71, 73, 78] Rimonabant dPAG Ultrasom-induced hyperlocomotion and freezing 30g No effect by itself [70] AEA uptake inhibitor AM404 dlPAG EPM 0.5–50 pmol No effect by itself; potentiated the anxiolytic effect of AEA [71] VCT 50 pmol Anxiolytic [73] CFC 50 pmol Anxiolytic [78] AEA metabolism inhibitor URB597 dlPAG VCT 0.01–0.1 nmol Anxiolytic (0.01 pmol*) [73] TRPV1 antagonists Capsazepine dlPAG EPM, VCT 10–60 nmol Anxiolytic (60 nmol)+ [87]

*Bell-shaped dose-response curve. Anxiolytic effect blocked by AM251 (100 pmol) and potentiated by AM404 (50 pmol).+Capsazepine 10 nmol turned the higher, ineffective dose of CBD (60 nmol) into an anxiolytic one in the EPM [85].**Not blocked by rimonabant 30g.