Fig. 2.

Effects of haloperidol on basal antinociception and morphine antinociception (A–C) and locomotor activity in naive (D) and morphine-tolerant (E) mice. A, separate groups of six mice received haloperidol (Halo; 0.1, 0.3, or 1 mg/kg i.p.) or an equal volume of saline 30 min before the tail-flick test (left columns). Additional groups of six mice were pretreated with saline or haloperidol (0.1, 0.3, or 1 mg/kg i.p.) 30 min before a test dose of morphine (MS; 3 mg/kg s.c.) for antinociception test. Haloperidol at these doses (0.1–1 mg/kg) did not by itself produce antinociception or alter morphine antinociception. B, time course for the effect of haloperidol (0.1, 0.3, or 1 mg/kg i.p.) and saline in the tail-flick test. C, time course for the effect of haloperidol (0.1, 0.3, or 1 mg/kg i.p.) on antinociception produced by morphine (3 mg/kg s.c.). A to C, n = 6/group. D, effect of haloperidol on locomotor activity in naive mice. For the rotarod test, mice were trained to remain on a fixed speed (4 rpm) rotarod for 60 s. On the next day, mice were retrained, and baseline was obtained by placing mice on an accelerating rotarod (4–40 rpm over 300 s). Mice were then treated with haloperidol (1.0 mg/kg i.p.) or saline and retested 1, 2, and 4 h later. The latency to fall off of the rotarod was recorded. n = 6/group. No significant difference was identified. E, effect of haloperidol on locomotor activity in morphine-tolerant mice. Mice received a twice daily injection of morphine (10 mg/kg) to induce tolerance. Mice were trained on day 4, and the rotarod test was tested on day 5 as described above. Mice were treated with saline, haloperidol (1 mg/kg i.p.), haloperidol (1 mg/kg i.p.), and morphine (10 mg/kg s.c.), or MK801 (1 mg/kg i.p.). The latter is an NMDA receptor antagonist that is known to impair locomotor activity and was used as a positive control. n = 6 for each test group and 12 for the saline group. *, p < 0.05; **, p < 0.01; ***, p < 0.001 compared with the saline group.