Antiaversive Effects of Cannabinoids: Is the Periaqueductal Gray Involved?

Table 1

Effects of cannabinoids and drugs that interfere with the endocannabinoid system in animal models predictive of anxiolytic- or anxiogenic-like activity. (AEA: AEA; Δ⁹-THC: Δ⁹-tetrahydrocannabinol; CBD: cannabidiol; EPM: elevated plus-maze; EXM: elevated X-maze; EZM: elevated zero-maze; VCT: Vogel conflict test; FC: fear conditioning; DLT: dark-light test; SI: social; NSF: novelty-suppressed feeding interaction.)

Drug	Test	Dose (species)		Reference
		Anxiolytic-like effects	Anxiogenic-like effects
Phytocannabinoids
Δ^9-THC	EPM		10–20 mg/kg (mouse)	[37]
	EPM		1–10 mg/kg (rat)	[37]
	DLT	0.3 mg/kg (mouse)	0.5 mg/kg (mouse)	[38]
	DLT	0.3 mg/kg (mouse)		[39]
	EPM		1–10 mg/kg (mouse)	[40]
	EPM	0.075–0.75 mg/kg (rat)		[41]
	EPM		0.5–2.5 mg/kg (rat)	[42]
	DLT		1.25–2.5 mg/kg (rat)	[42]
	EPM	0.075–1.5; 3^* mg/kg (rat)		[43]
CBD	EPM	1–10 mg/kg (mouse)		[37]
	EPM	2.5–10; 20^* mg/kg (rat)		[44]
	EPM	5 mg/kg (rat)		[45]
	VCT	10 mg/kg (rat)		[46]
	FC	10 mg/kg (rat)		[47]
CB1 agonists
HU210	EXM		25𝜇g/kg, 10 days (rat)	[48]
	NSF	100𝜇g/kg/day–10 days (rat)		[49]
	EPM	10𝜇g/kg (rat)	50𝜇g/kg (rat)	[50]
WIN-55212	EPM	1–3 mg/kg (mouse)		[51]
	EPM	1–3; 10^* mg/kg (mouse)		[40]
	EPM	1–3 mg/kg (mouse)	1–3 mg/kg (rat)	[52]
CP55940	EPM		75–125𝜇g/kg (rat)	[53]
	EPM		75𝜇g/kg (rat)	[54]
	EPM	1𝜇g/kg (rat)	50𝜇g/kg (rat)	[55]
	EPM	2.5–5𝜇g/kg (rat)	40𝜇g/kg (rat)	[56]
	SI		40𝜇g/kg (rat)	[57]
	EPM	0.1–0.3 mg/kg (mouse)		[40]
AEA	EPM		10 mg/kg (mouse)	[58]
	DLT	0.3 mg/kg (rat)		[59]
AEA uptake inhibitor
AM404	EPM	5 mg/kg (rat)		[60]
	EPM	1–3; 10^* mg/kg (mouse)		[40]
	EPM	0.75–1.25 mg/kg (rat)		[37]
AEA metabolism inhibitors
URB597	EZM	0.1 mg/kg (rat)		[61]
	EPM	0.1–0.3 mg/kg (mouse)		[40]
	EPM	0.1 mg/kg (mouse)		[62]
	DLT	0.1–0.3 mg/kg (rat)		[55]
	EPM	1 mg/kg (mouse)		[63]
AACOCF3	DLT	4 mg/kg (mouse)		[64]
CB1 antagonists
Rimonabant	EPM		3 mg/kg (rat)	[65]
	EPM		3 mg/kg (rat)	[53]
	EPM	3 mg/kg (mouse)		[66]
	VCT	0.3–3 mg/kg (rat)		[67]
	EPM	10 mg/kg (rat)		[67]
	EPM		3–10 mg/kg (mouse)	[40]
AM251	EPM		3 mg/kg (mouse)	[51]
	EPM		1.3–3 mg/kg (mouse)	[68]
	EPM		3–10 mg/kg (mouse)	[40]
	EPM		1–3 mg/kg (mouse)	[52]
TRPV1 agonists
Olvanil	EPM	5 mg/kg (rat)		[69]
TRPV1 antagonists
Capzasepine	EPM	1–10𝜇g/kg (rat)		[69]

^*Bell-shaped dose-response curve.