TY - JOUR
T1 - 3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") and its stereoisomers as reinforcers in rhesus monkeys
T2 - Serotonergic involvement
AU - Fantegrossi, William E.
AU - Ullrich, Thomas
AU - Rice, Kenner C.
AU - Woods, James H.
AU - Winger, Gail
N1 - Funding Information:
Acknowledgements These studies were supported by USPHS Grants DA09161 and DA05923. The authors express their gratitude for the expert technical assistance provided by Amy Foster, Deborah Huntzinger, Sarah Pilkington, and Jolan Terner.
PY - 2002
Y1 - 2002
N2 - Rationale: The reinforcing effects of MDMA and its enantiomers have not been extensively characterized in laboratory animals. Objectives: To investigate whether MDMA and its stereoisomers would be self-administered intravenously by rhesus monkeys (Macaca mulatta), and to assess the effects of serotonin2 receptor antagonists on MDMA-maintained responding. Methods: Four adult male rhesus monkeys were maintained on a fixed ratio 10, time-out 60-s schedule for 0.01 mg/kg cocaine or saline injections. Racemic MDMA and its stereoisomers, and racemic methamphetamine were periodically substituted for cocaine or saline. In subsequent antagonist experiments, five adult rhesus monkeys (three male, two female) were maintained on a multiple dose fixed ratio 30, time-out 45-s schedule for cocaine or saline injections. Racemic MDMA and its enantiomers were periodically substituted for cocaine or saline, with or without a pre-session injection of the serotonin2 receptor antagonists ketanserin or MDL100907. Results: In the initial self-administration experiments, MDMA and its stereoisomers generated "inverted U"-shaped self-administration curves across the dose range tested. Racemic MDMA doses between 0.01 and 0.1 mg/kg per injection, S(+)-MDMA doses between 0.003 and 0.1 mg/kg per injection, and R(-)-MDMA doses between 0.01 and 0.1 mg/kg per injection engendered more responding than saline; however, no dose of any form of MDMA maintained as much behavior as cocaine or methamphetamine. In subsequent antagonist experiments, pretreatments with 0.1 or 0.3 mg/kg ketanserin or MDL100907 attenuated responding for S(+)-MDMA, and completely abolished responding for R(-)-MDMA, but did not affect cocaine-maintained behavior. Conclusions: MDMA and its stereoisomers serve as reinforcers in rhesus monkeys. We suggest that stimulation of 5-HT2A receptors is integral to the reinforcing effects of MDMA.
AB - Rationale: The reinforcing effects of MDMA and its enantiomers have not been extensively characterized in laboratory animals. Objectives: To investigate whether MDMA and its stereoisomers would be self-administered intravenously by rhesus monkeys (Macaca mulatta), and to assess the effects of serotonin2 receptor antagonists on MDMA-maintained responding. Methods: Four adult male rhesus monkeys were maintained on a fixed ratio 10, time-out 60-s schedule for 0.01 mg/kg cocaine or saline injections. Racemic MDMA and its stereoisomers, and racemic methamphetamine were periodically substituted for cocaine or saline. In subsequent antagonist experiments, five adult rhesus monkeys (three male, two female) were maintained on a multiple dose fixed ratio 30, time-out 45-s schedule for cocaine or saline injections. Racemic MDMA and its enantiomers were periodically substituted for cocaine or saline, with or without a pre-session injection of the serotonin2 receptor antagonists ketanserin or MDL100907. Results: In the initial self-administration experiments, MDMA and its stereoisomers generated "inverted U"-shaped self-administration curves across the dose range tested. Racemic MDMA doses between 0.01 and 0.1 mg/kg per injection, S(+)-MDMA doses between 0.003 and 0.1 mg/kg per injection, and R(-)-MDMA doses between 0.01 and 0.1 mg/kg per injection engendered more responding than saline; however, no dose of any form of MDMA maintained as much behavior as cocaine or methamphetamine. In subsequent antagonist experiments, pretreatments with 0.1 or 0.3 mg/kg ketanserin or MDL100907 attenuated responding for S(+)-MDMA, and completely abolished responding for R(-)-MDMA, but did not affect cocaine-maintained behavior. Conclusions: MDMA and its stereoisomers serve as reinforcers in rhesus monkeys. We suggest that stimulation of 5-HT2A receptors is integral to the reinforcing effects of MDMA.
KW - Amphetamine
KW - MDMA
KW - Rhesus monkey
KW - Self-administration
KW - Serotonin antagonist
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U2 - 10.1007/s00213-002-1021-6
DO - 10.1007/s00213-002-1021-6
M3 - Article
C2 - 12073162
AN - SCOPUS:0035987117
VL - 161
SP - 356
EP - 364
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 4
ER -