912342-28-0

In an initial dose-response study, TCB2 (0.5, 1.0, and 2.5 mg/kg) and DOI (0.5, 1.0, 2.5, and 5.0 mg/kg) induce head twitches in C57BL/6J mice in a dose-dependent manner compared to vehicle. Head twitches induced by TCB2 and DOI are similar across the doses, with the exception that at the highest dose (5.0 mg/kg), TCB2 induces half as many head twitches as does DOI (p=0.021). Confirming 5-HT2A mediation of the head twitch response, in two separate studies, pretreatment with the selective 5-HT_2A antagonist MDL 11,939 (1.0 mg/kg) block head twitches induced by DOI (2.5 mg/kg) and by TCB2 (2.5 mg/kg; p<0.0001). Compared to vehicle, corticosterone levels are increased following TCB2 (5.0 mg/kg, p=0.01; 10.0, p=0.012; with a trend following 2.5 mg/kg, p=0.079) and DOI (10.0 mg/kg, p=0.035)^[1].