Findings from the current investigation also complement previous animal studies which have demonstrated alterations in behavior in genetically altered animals and those which administer both low (Cherek et al., 1980) and high doses (Alves et al., 1973) of THC. Animal studies have reported that the administration of cannabinoids can induce both anxiogenic and anxiolytic response, depending on both the dose administered and the familiarity of the animal to its environment (Rodriguez de Fonseca et al., 1996). Specifically, low doses appear to produce anxiolytic-like responses while higher doses result in more anxiogenic-like behaviors, including increased muricidal behavior (Bac et al., 1998). In one recent study of CB-1 knockout mice, increased aggressive behavior was noted following a resident-intruder procedure, where an animal is exposed to a novel, or intruding animal for four minutes, relative to wild-type animals (Martin et al., 2002), underscoring the relationship between CB-1 receptors and behaviors related to anxiety. Hill and colleagues (2006) examined the effects of administering both a very low (5 µg/kg) and very high (100 µg/kg) dose of the cannabinoid CB1 agonist HU-210 in rats, and
