Tolerance and cross-tolerance to 3,4-methylenedioxymethamphetamine (MDMA), methamphetamine and methylenedioxyamphetamine.

The effects of (+-)-3,4-methylenedioxymethamphetamine (MDMA) (0.62-20.0 mg/kg), (+)-methamphetamine (MA) (0.62-5.0 mg/kg) and (+/-)-3,4-methylenedioxyamphetamine (MDA) (0.62-5.0 mg/kg) on milk intake in rats were determined before and during a period of repeated daily administration of MDMA. Experimental sessions consisted of 15-min access to a sweetened milk solution each day, 5 days a week. After initial determination of the effects of MDMA, MA and MDA on milk intake, rats were injected daily with either MDMA (2.5-5.0 mg/kg) or saline. Two groups of rats were injected with MDMA, one group 15 min before, and the other group 15 min after the milk-drinking sessions. Two more groups of rats were injected with saline, one group 15 min before, and the other group 15 min after the sessions. During this repeated administration period the effects of MDMA, MA and MDA (injected 15 min prior to the session) were redetermined. In rats that had been injected with MDMA on a daily basis either before or after the milk-drinking sessions, the dose-response function of MDMA was shifted to the right, indicating that tolerance had developed. Cross-tolerance to MA appeared to develop only in the group of rats that had been injected with MDMA on a daily basis before the milk-drinking sessions. Cross-tolerance to MDA did not develop in any of the 4 groups of rats.