Atypical development of behavioural sensitization to 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') in adolescent rats and its expression in adulthood: role of the MDMA chirality.
Despite the great popularity of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) as a drug of abuse, not much is known about the detailed mechanisms of the acute and subchronic effects of the drug. There is especially a lack of information about the distinct behavioural effects of its optical isomers (enantiomers) R- and S-MDMA compared with the racemic RS-MDMA. For this purpose, adolescent rats were repetitively treated during two treatment stages (stage 1: days 1-10; stage 2: days 15, 17, 19) with RS-MDMA (5 or 10 mg/kg) or each of the respective enantiomers (5 mg/kg). The repeated treatment started on postnatal day (PND) 32 and locomotor activity was measured on each day by means of a photobeam-equipped activity box system. RS-MDMA or S-MDMA administration led acutely to massive hyperlocomotion and subchronically, to the development of behavioural sensitization after a short habituation period. R-MDMA was free of hyperactivating effects and even decreased locomotor behaviour upon repeated treatment. Nevertheless, co-administration of R-MDMA increased the hyperactivity of S-MDMA and made the S-MDMA induced behavioural sensitization state-dependent. The animals pre-treated with R-MDMA showed a sensitized response in adulthood when tested with RS-MDMA. Our results indicated that even in the absence of substantial neurotoxicity, both MDMA enantiomers can lead to long-term changes in brain circuitry and concomitant behavioural changes when repeatedly administered in adolescence. The sensitization development was most pronounced in the animals treated with S- and RS-MDMA; the animals with R-MDMA did not develop sensitization under repeated treatment but expressed a sensitized response when challenged with RS-MDMA.
von Ameln
Nora
N
University of Tuebingen, Neuropharmacology, Auf der Morgenstelle 28E, Tuebingen, Germany. nora.von-ameln@uni-tuebingen.de
von Ameln-Mayerhofer
Andreas
A
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D006213:Hallucinogens / Q000633:toxicity*; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D013287:Illicit Drugs / Q000633:toxicity*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism; D013237:Stereoisomerism
D006213:Hallucinogens; D013287:Illicit Drugs; D015102:3,4-Dihydroxyphenylacetic Acid; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D004298:Dopamine