Behavioral effects of the imidazoline I(2) receptor ligand BU99006 in rats

Abstract

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.

Fig. 1

Hypothermic effects of BU99006 alone (left) or in combination with 2-BFI (middle) or idazoxan (right). Ordinates, body temperature changes ± SEM (°C). Abscissa, time after drug administration (min). * P < 0.05 as compared to 10 mg/kg BU99006 alone. Unit of drug doses: mg/kg.

Fig. 2

Discriminative stimulus (top panel) and response rate-altering (bottom panel) effects of 2-BFI and BU99006, alone (left panels) or in combination (right panels), in rats discriminating 5.6 mg/kg 2-BFI from saline (n = 8). Ordinates: top panels, average percentage of responses on the 2-BFI-associated lever ± SEM; bottom panels, average response rate ± SEM in responses per second. Abscissa: dose in mg/kg body weight. ‘V’ indicates vehicle. * P < 0.05 as compared to Vehicle; ^$ P < 0.05 as compared to 2-BFI alone. See Fig. 1 for other details.