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The imidazoline I2 receptor ligand BU99006 binds to and attenuates effects mediated by I2 receptors in vitro, although its effects in vivo have not been studied previously. This study examined the effects of BU99006 in two behavioral assays in rats: hypothermia and 2-BFI discrimination. BU99006 (3.2–15 mg/kg, intraperitoneally) produced a dose-dependent hypothermic effect (rectal temperature), which was antagonized by the I2 receptor antagonist idazoxan. BU99006 (3.2 or 10 mg/kg administered 10 min or 2 h before the session, respectively) did not significantly alter hypothermia produced by the I2 receptor agonist 2-BFI (10 mg/kg). In rats discriminating 5.6 mg/kg 2-BFI, BU99006 (1.78–17.8 mg/kg, intraperitoneally) produced 40 and 82% responding on the 2-BFI-associated lever when it was administered immediately or 2 h before the test sessions, respectively. BU99006 enhanced the discriminative stimulus and rate-suppressing effects of 2-BFI. Collectively, these data suggest that BU99006 is an imidazoline I2 receptor agonist with no evidence of I2 receptor antagonism in rats.
