These results establish the specificity of AM3506′s effects on extinction and not other fear-related processes. However, previous rodent studies have shown that pharmacological manipulation of the endocannabinoid system has effects on locomotion, depression-related behavior and feeding.7 We therefore examined the effects of systemic AM3506 treatment, using the same 1 mg/kg dose, route and injection-test interval as we found facilitated extinction, on measures of these behaviors. Relative to vehicle, AM3506 treatment did not alter spontaneous locomotion (Figure 1g), ‘depression-related’ immobility in the forced swim test (Figure 1h) or food consumption after overnight fasting (Figure 1i) (all t-tests: P>0.05, n = 8). We also found that AM3506 did not promote glucose intolerance in anandamide-treated mice, an effect that contrasted with the pro-intolerance effect of URB597, replicating a dissociation between these compounds previously observed in diet-induced obese mice19 (Supplementary Figure S3). Taken together, these negative findings provide further support for the behavioral specificity of AM3506, although testing across a broad range of assays will be needed be provide a full pharmacodynamic profile of the drug.
