Reinstatement of extinguished amphetamine self-administration by 3,4-methylenedioxymethamphetamine (MDMA) and its enantiomers in rhesus monkeys. 2010

Jessica McClung, and William Fantegrossi, and Leonard L Howell
Division of Neuroscience, Yerkes National Primate Research Center, Emory University, Atlanta, GA, USA.

BACKGROUND The effectiveness of MDMA and its enantiomers to reinstate responding previously maintained by drug self-administration has not been thoroughly investigated. OBJECTIVE The present study was designed to compare the reinstatement effects of amphetamine, the piperazine-analog BZP, SR(+/-)-MDMA, S(+)-MDMA, R(-)-MDMA, and fenfluramine on behavior maintained under a second-order schedule of intravenous amphetamine self-administration in rhesus monkeys (n=4). METHODS Following saline substitution and extinction, a range of doses of amphetamine, BZP, SR(+/-)-MDMA, S(+)-MDMA, R(-)-MDMA, and fenfluramine were administered i.v. as non-contingent priming injections in order to characterize their effectiveness to reinstate responding previously maintained by amphetamine self-administration. RESULTS Priming injections of amphetamine, BZP, SR(+/-)-MDMA, and S(+)-MDMA induced significant reinstatement effects. In contrast, neither R(-)-MDMA nor fenfluramine effectively reinstated behavior. Pretreatment with the selective serotonin transporter inhibitor, fluoxetine, attenuated the reinstatement effects of SR(+/-)-MDMA, S(+)-MDMA, and BZP but had no significant effect on amphetamine-primed reinstatement. CONCLUSIONS Given the profile of neurochemical effects published previously, these findings suggest that the reinstatement effects of MDMA are mediated primarily by dopamine release; however, the attenuation of MDMA-induced reinstatement by fluoxetine supports previous research demonstrating the complex behavioral pharmacology of MDMA-like drugs and that the reinstatement effects of MDMA are at least partially mediated by serotonergic mechanisms.

UI MeSH Term Description Entries
D008253 Macaca mulatta A species of the genus MACACA inhabiting India, China, and other parts of Asia. The species is used extensively in biomedical research and adapts very well to living with humans. Chinese Rhesus Macaques,Macaca mulatta lasiota,Monkey, Rhesus,Rhesus Monkey,Rhesus Macaque,Chinese Rhesus Macaque,Macaca mulatta lasiotas,Macaque, Rhesus,Rhesus Macaque, Chinese,Rhesus Macaques,Rhesus Macaques, Chinese,Rhesus Monkeys
D011930 Reaction Time The time from the onset of a stimulus until a response is observed. Response Latency,Response Speed,Response Time,Latency, Response,Reaction Times,Response Latencies,Response Times,Speed, Response,Speeds, Response
D012055 Reinforcement Schedule A schedule prescribing when the subject is to be reinforced or rewarded in terms of temporal interval in psychological experiments. The schedule may be continuous or intermittent. Reinforcement Schedules,Schedule, Reinforcement,Schedules, Reinforcement
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D005260 Female Females
D000661 Amphetamine A powerful central nervous system stimulant and sympathomimetic. Amphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulation of release of monamines, and inhibiting monoamine oxidase. Amphetamine is also a drug of abuse and a psychotomimetic. The l- and the d,l-forms are included here. The l-form has less central nervous system activity but stronger cardiovascular effects. The d-form is DEXTROAMPHETAMINE. Desoxynorephedrin,Levoamphetamine,Phenopromin,l-Amphetamine,Amfetamine,Amphetamine Sulfate,Amphetamine Sulfate (2:1),Centramina,Fenamine,Mydrial,Phenamine,Thyramine,levo-Amphetamine,Sulfate, Amphetamine,l Amphetamine,levo Amphetamine
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D012646 Self Administration Administration of a drug or chemical by the individual under the direction of a physician. It includes administration clinically or experimentally, by human or animal. Administration, Self,Administrations, Self,Self Administrations
D013237 Stereoisomerism The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed) Molecular Stereochemistry,Stereoisomers,Stereochemistry, Molecular,Stereoisomer
D018817 N-Methyl-3,4-methylenedioxyamphetamine An N-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as MDMA or ecstasy. MDMA,Methylenedioxymethamphetamine,Ecstasy (Drug),N-Methyl-3,4-methylenedioxyamphetamine Hydrochloride,Hydrochloride, N-Methyl-3,4-methylenedioxyamphetamine,N Methyl 3,4 methylenedioxyamphetamine,N Methyl 3,4 methylenedioxyamphetamine Hydrochloride

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