Behavioral effects of (+-) 3,4-methylenedioxyamphetamine (MDA) and (+-) 3,4-methylenedioxymethamphetamine (MDMA) in the pigeon: interactions with noradrenergic and serotonergic systems.

The effects of three amphetamine analogs were assessed in pigeons key pecking under a multiple 3-min fixed-interval (FI), 30 response fixed-ratio (FR) schedule of food presentation. At doses between 0.1 and 10.0 mg/kg, (+-) 3,4-methylenedioxyamphetamine (MDA), (+-) 3,4-methylenedioxymethamphetamine (MDMA), and (+-)-N-ethyl-3,4-methylenedioxyamphetamine (MDE) either had no effect or decreased response rates in both components of the multiple schedule in a dose-dependent manner. MDA was at least 1 log unit more potent than the other two compounds. Metergoline (0.1-1.0 mg/kg), a serotonin (5-HT) antagonist with comparable affinity for the 5-HT1 and 5-HT2 receptor subtypes, blocked the rate-decreasing effects of 3.0 mg/kg MDA in both components of the multiple schedule, but did not affect the MDMA dose-response curve. The 5-HT2 receptor antagonist ketanserin (0.1-3.0 mg/kg) also restored FI and FR responding that was decreased by 3.0 mg/kg MDA, but had no effect on responding suppressed by MDMA. The noradrenergic alpha-1 antagonist prazosin (0.3-3.0 mg/kg) blocked the behavioral effects of 3.0 mg/kg MDMA at doses that did not attenuate MDA's rate-decreasing effects. These results indicate that although MDA and MDMA are structurally similar and have similar behavioral effects, their actions appear to be mediated through different neurotransmitter systems.