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Atypical development of behavioural sensitization to 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') in adolescent rats and its expression in adulthood: role of the MDMA chirality.
Addict Biol. 2010 Jan; 15(1):35-44.AB

Abstract

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.

Authors+Show Affiliations

University of Tuebingen, Neuropharmacology, Auf der Morgenstelle 28E, Tuebingen, Germany. nora.von-ameln@uni-tuebingen.deNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20002021

Citation

von Ameln, Nora, and Andreas von Ameln-Mayerhofer. "Atypical Development of Behavioural Sensitization to 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') in Adolescent Rats and Its Expression in Adulthood: Role of the MDMA Chirality." Addiction Biology, vol. 15, no. 1, 2010, pp. 35-44.
von Ameln N, von Ameln-Mayerhofer A. Atypical development of behavioural sensitization to 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') in adolescent rats and its expression in adulthood: role of the MDMA chirality. Addict Biol. 2010;15(1):35-44.
von Ameln, N., & von Ameln-Mayerhofer, A. (2010). Atypical development of behavioural sensitization to 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') in adolescent rats and its expression in adulthood: role of the MDMA chirality. Addiction Biology, 15(1), 35-44. https://doi.org/10.1111/j.1369-1600.2009.00187.x
von Ameln N, von Ameln-Mayerhofer A. Atypical Development of Behavioural Sensitization to 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') in Adolescent Rats and Its Expression in Adulthood: Role of the MDMA Chirality. Addict Biol. 2010;15(1):35-44. PubMed PMID: 20002021.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Atypical development of behavioural sensitization to 3,4-methylenedioxymethamphetamine (MDMA, 'Ecstasy') in adolescent rats and its expression in adulthood: role of the MDMA chirality. AU - von Ameln,Nora, AU - von Ameln-Mayerhofer,Andreas, PY - 2009/12/17/entrez PY - 2009/12/17/pubmed PY - 2010/3/17/medline SP - 35 EP - 44 JF - Addiction biology JO - Addict Biol VL - 15 IS - 1 N2 - 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. SN - 1369-1600 UR - https://www.unboundmedicine.com/medline/citation/20002021/Atypical_development_of_behavioural_sensitization_to_34_methylenedioxymethamphetamine__MDMA_'Ecstasy'__in_adolescent_rats_and_its_expression_in_adulthood:_role_of_the_MDMA_chirality_ L2 - https://doi.org/10.1111/j.1369-1600.2009.00187.x DB - PRIME DP - Unbound Medicine ER -