Several lines of evidence suggest that acute enhancement of CB1R activity results in antidepressant- and anxiolytic-like effects in rodents (Table 1). For example, activation of CB1R by administration of its agonists HU210 or oleamide resulted in antidepressant-like action in the rat FST model [68]. Similar antidepressant and/or anxiolytic effects were observed after acute activation of CB1R by THC [69,70] or other cannabinoids, such as the synthetic agonists WIN55, 212–2 [71], CP55, 940 [72], as well as the endogenous AEA [73,74]. Other cannabinoid agonists or partial agonists, endogenous and exogenous, also showed similar effects (reviewed in [10,67]). The efficacy of these cannabinoid compounds was as good as some known antidepressants with which they were compared. In most cases, these positive effects on anxiety and depression were observed at relatively low doses of cannabinoids activating CB1R, whereas higher doses were often pro-depressive and anxiogenic [69,75,76,77,78,79]. This observation could mirror the biphasic effects usually seen in humans [10,69]. There are, however, some reported differences, which were essentially explained by species (mouse vs. rat) and strain differences, the brain region injected or studied, the test used, or other experimental differences [10,67].
