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Chunk #21 — 4. Discussion

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Inhibition of endocannabinoid catabolic enzymes elicits anxiolytic-like effects in the marble burying assay.
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In the present studies, JZL184 caused a significant decrease in marble burying but also increased immobility at the highest dose tested (i.e., 40 mg/kg). Unlike diazepam or THC, however, this increase in immobility was not apparent until 10 min into the test session. These data somewhat contrast with our previous report that JZL184 causes a decrease in spontaneous locomotor activity (Long et al., 2009), however, this discrepancy is likely due to differences in the vehicle used. The original study used a vehicle consisting of 4:1 parts polyethylene glycol (PEG200):TWEEN80) and the present study used a vehicle consisting of 1:1:18 parts ethanol, Alkamuls-620, and saline. Supporting this notion, when dissolved in the same vehicle used in the present study, JZL184 had no effect on muscle coordination in the rotarod test (Schlosburg et al., 2009). Moreover, in the same experiment, high doses of THC disrupted motor coordination. Thus, high doses of JZL184 may produce hypomotility, but not sedation or loss of muscle coordination.