Reinforcing effects of methylenedioxy amphetamine congeners in rhesus monkeys: are intravenous self-administration experiments relevant to MDMA neurotoxicity?
BACKGROUND
Many animal models relevant to the persistent effects of drugs of abuse necessitate the application of interspecies dose scaling procedures to approximate drug administration regimens in humans, but drug self-administration procedures differ in that they allow animal subjects to control their own drug intake.


OBJECTIVE
This report reviews the reinforcing effects of 3,4-methylenedioxymethamphetamine (MDMA), its enantiomers, and several structural analogs in rhesus monkeys, paying particular attention to the pharmacological mechanisms of such reinforcing effects, the development of structure activity relationships among these compounds, the stability of MDMA self-administration behavior over time, and the persistent effects of self-administered MDMA on monoamines.


RESULTS
The methylenedioxy amphetamine congeners MDMA, 3,4-methylenedioxyamphetamine, N-ethyl-3,4-methylenedioxyamphetamine, and N-methyl-1-(3,4-methylenedioxyphenyl)-2-butanamine function as reinforcers in rhesus monkeys, maintaining self-administration behavior greater than that engendered by contingent saline but less than that engendered by traditional psychostimulants. These findings are remarkable as structurally distinct serotonergic hallucinogen-like drugs do not maintain reliable self-administration in laboratory animals. During prolonged MDMA self-administration, MDMA-maintained responding progressively weakens, and MDMA eventually fails to maintain significant self-administration. The neurochemical correlates of this effect have not yet been identified.


CONCLUSIONS
Procedures in which MDMA and related compounds are self-administered can be established in rhesus monkeys. These techniques can be used to engender contingent MDMA exposure without resorting to controversial methods of interspecies dose scaling. As such, further application of self-administration methods may provide important new insights into the persistent effects of MDMA on brain and behavior in nonhuman primates.
Division of Neuroscience, Yerkes National Primate Research Center, Emory University, 954 Gatewood Road, Atlanta, GA 30322, USA. wfanteg@emory.edu
William E
WE
Fantegrossi
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006213:Hallucinogens / Q000008:administration & dosage / Q000633:toxicity; D007275:Injections, Intravenous; D008253:Macaca mulatta; D023421:Models, Animal; D015394:Molecular Structure; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000737:chemistry / Q000633:toxicity*; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000378:metabolism; D012054:Reinforcement, Psychology; D012646:Self Administration; D013329:Structure-Activity Relationship
D015306:Biogenic Monoamines; D006213:Hallucinogens; D018817:N-Methyl-3,4-methylenedioxyamphetamine