Cannabinoid Mediated Diuresis In Mice

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Cannabinoid (CB) receptor agonists increase urinary output in rats however these effects have not been characterized in mice. This study investigates whether diuresis is a CB receptor mediated effect in mice, and further compares CB mediated diuresis with CB induced analgesia. Adult male CD1 mice were injected sc (10 ml/kg) with vehicle or novel and commercially available CB agonists (AM4054, AM7418, 9THC and WIN55212 -22). Voided urine was measured over 6hr using single dosing procedures. Analgesia was measured using cumulative dosing procedures and a hot water (52°C) tail-withdrawal assay (8-sec cut-off, baseline latency = 2.2±0.11 sec). In antagonism studies, 0.1—10.0 mg/kg SR141716A was administered as a 30min pretreatment. All of the CB agonists increased diuresis, yielding biphasic dose response curves with maximum voided urine ranging from 28—35 g/kg; urine output after vehicle injection ranged from 5—12 g/kg. All CB agonists also increased analgesia dose-dependently with peak effects similar to morphine. Peak diuretic effects occurred at doses approximately log unit lower than those that produced maximum analgesic effects. SR141617A dose dependently shifted the diuretic and analgesic dose response curve of AM4054 to the right, and was marginally more potent in the diuresis assay. Our results indicate that CB agonists produce diuresis by acting on CB1 receptors.

Source: Cannabinoid mediated diuresis in mice -- Chopda et al. 25 (1): 617.6 -- The FASEB Journal