5-HT_2AR does not mediate THC-induced hypolocomotion, hypothermia, analgesia, anxiogenic-like behavior, or the reinforcing properties of WIN 55,212–2.

<p>(A) Locomotor activity (% of baseline) was dose-dependently reduced in both WT and 5-HT_2AR KO mice treated with THC (0.3, 1, 3, and 10 mg/kg) as compared to vehicle (VEH) administration (<i>n</i> = 5–15). (B) THC induced hypothermia at the dose of 10 mg/kg to a similar extent in WT and 5-HT_2AR KO mice (<i>n</i> = 13–24). (C) In the tail-immersion test, percent analgesia was dose-dependently increased by THC (1, 3, and 10 mg/kg) in both WT and 5-HT_2AR KO mice (<i>n</i> = 10–16). In the hot-plate test, the percent of analgesia as calculated from the latency to paw-licking (D) and to jumping behavior (E) was similar in WT and KO animals treated with THC (1, 3, and 10 mg/kg) as compared to VEH administration (<i>n</i> = 7–16). (F) No significant differences between genotypes were observed in anxiogenic-like behavior induced by THC (3 mg/kg) (<i>n</i> = 6–10). (G) Both WT and 5-HT_2AR KO mice acquired WIN 55,212–2 self-administration behavior and responded equally for this drug during the 12 d of training (<i>n</i> = 12–15). Data are mean + SEM. * <i>p</i> < 0.05, ** <i>p</i> < 0.01, and *** <i>p</i> < 0.001 versus VEH-treated animals. The statistical analyses used and their corresponding F and <i>p</i>-values are shown in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1002194#pbio.1002194.s013" target="_blank">S1 Table</a>.