Review Article
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;
-THC:
-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 | | | | |
| -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 | | 25g/kg,
10 days (rat) | [48] | NSF | 100g/kg/day–10 days (rat) | | [49] | EPM | 10g/kg
(rat) | 50g/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 | | 75–125g/kg
(rat) | [53] | EPM | | 75g/kg
(rat) | [54] | EPM | 1g/kg
(rat) | 50g/kg
(rat) | [55] | EPM | 2.5–5g/kg
(rat) | 40g/kg
(rat) | [56] | SI | | 40g/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 | 1–10g/kg
(rat) | | [69] |
|
|
*Bell-shaped dose-response curve.
|