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.
Nader
M A
MA
Behavioral Pharmacology Laboratory, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814-4799.
Hoffmann
S M
SM
Barrett
J E
JE
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D010856:Columbidae; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D009638:Norepinephrine / Q000502:physiology; D011224:Prazosin / Q000494:pharmacology; D012055:Reinforcement Schedule; D012701:Serotonin / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000502:physiology*
D000662:Amphetamines; D008711:Metergoline; D012701:Serotonin; D015104:3,4-Methylenedioxyamphetamine; D007650:Ketanserin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C051800:3,4-methylenedioxyethamphetamine; D009638:Norepinephrine; D011224:Prazosin