Fig. 3. 5-HT_2AR activity may be necessary but not sufficient for the development of social sensitization.

(a) Pretreatment with the 5-HT_2AR antagonist M100 (1 mg/kg) on days 1, 3, and 5 inhibited the development of social sensitization in MDMA treated mice. On day 7 when mice were tested for social interaction without pretreatments, mice that had received M100 during the previous treatment sessions interacted significantly less than mice that had received saline pretreatments during those days. (b) When M100 was administered before MDMA on day 7 to mice that had received MDMA without pretreatments on the three previous test days, M100 did not attenuate MDMA-induced social interaction. Therefore, at this dose M100 does not appear to inhibit the expression of MDMA-induced social behavior in mice that are already sensitized. (c) M100 did not significantly affect locomotor activity relative to saline. (d) Treatment with the 5-HT_2AR agonist DOI (1 mg/kg) during test days 1, 3, and 5 did not sensitize mice to MDMA-induced social interaction when it was administered on day 7. Treatment with a 5-HT_2AR agonist therefore appears insufficient to sensitize mice to the prosocial effects of MDMA. Symbols indicate that social interaction was significantly different (p < 0.05) from day 1 (ϕ) or that treatment day’s control group(s) (*).