Neural Plasticity / 2009 / Article / Tab 2 / Review Article
Antiaversive Effects of Cannabinoids: Is the Periaqueductal Gray Involved? 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dorsomedial) PAG; dmPAG: dorsomedial PAG; unpub: unpublished data.)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 0.1–5
g Attenuated flight
responses (0.1–5
g) [36 ] HU210 dmPAG Ultrasound-induced hyperlocomotion and freezing 5
g 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 30
g 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 30
g.