In this study, we examined the effect of the 5-HT2A,C receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) on locomotor activity and the head twitch response in rats by the repeated (twice daily for 4 days) subcutaneous administration of 0.9% saline (1 ml/kg) or (+/-)-3,4-Methylenedioxymethamphetamine (MDMA) (20 mg/kg), a compound that selectively destroys serotonergic nerve terminals. There was no difference between the MDMA- and saline-treated rats regarding the (+/-)-DOI-induced (0.625, 1.25 or 2.5 mg/kg, i.p.) increase and decrease in the head twitch response and horizontal locomotor activity, respectively. Overall, repeated MDMA does not alter the behavioral response of rats to (+/-)-DOI.