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Sensitization to MDMA locomotor effects and changes in the functionality of 5-HT(2A) and D₂ receptors in mice.
Behav Pharmacol. 2011 Aug; 22(4):362-9.BP

Abstract

The behavioral and neurochemical adaptations related to chronic 3,4-methylenedioxymethamphetamine (MDMA) treatment are largely unknown. In this study, we assessed whether repeated administration of MDMA would induce (a) context-dependent locomotor sensitization in mice and (b) changes in serotonin 5-HT(2A) and dopamine D₂ receptor functionality as measured by [³⁵S]GTPγS binding. Mice were treated with MDMA (10 mg/kg, intraperitoneally) or saline every other day for 11 days either in their home cages or in the environment where locomotor activity was measured. After a 10-day withdrawal period, mice were challenged with MDMA (5 and 10 mg/kg) and saline before locomotor activity measurements. During repeated MDMA treatment, locomotion was progressively enhanced, indicating the development of behavioral sensitization. The MDMA challenge at a dose of 5 mg/kg increased locomotor activity to a greater extent in mice pretreated with MDMA in the testing apparatus than in mice pretreated in the home cages, revealing that contextual cues paired with repeated drug exposure can enhance the expression of behavioral sensitization to MDMA. In contrast, a challenge administration of MDMA at 10 mg/kg induced similar locomotor sensitization in mice pretreated in both environments. An increase in the functionality of cortical 5-HT(2A) receptors was observed in mice pretreated with MDMA compared with mice pretreated with saline, but this activation was significantly greater in mice pretreated in the locomotor environment. In contrast, the functional activity of striatal D₂ receptors was significantly decreased only in mice pretreated with MDMA in the testing apparatus. These results reveal neuroadaptations in cortical 5-HT(2A) and striatal D₂ receptors after MDMA-induced behavioral sensitization in mice.

Authors+Show Affiliations

Universitat Pompeu Fabra, PRBB, Barcelona, Spain.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

21712712

Citation

Varela, María José, et al. "Sensitization to MDMA Locomotor Effects and Changes in the Functionality of 5-HT(2A) and D₂ Receptors in Mice." Behavioural Pharmacology, vol. 22, no. 4, 2011, pp. 362-9.
Varela MJ, Brea J, Loza MI, et al. Sensitization to MDMA locomotor effects and changes in the functionality of 5-HT(2A) and D₂ receptors in mice. Behav Pharmacol. 2011;22(4):362-9.
Varela, M. J., Brea, J., Loza, M. I., Maldonado, R., & Robledo, P. (2011). Sensitization to MDMA locomotor effects and changes in the functionality of 5-HT(2A) and D₂ receptors in mice. Behavioural Pharmacology, 22(4), 362-9. https://doi.org/10.1097/FBP.0b013e3283487346
Varela MJ, et al. Sensitization to MDMA Locomotor Effects and Changes in the Functionality of 5-HT(2A) and D₂ Receptors in Mice. Behav Pharmacol. 2011;22(4):362-9. PubMed PMID: 21712712.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sensitization to MDMA locomotor effects and changes in the functionality of 5-HT(2A) and D₂ receptors in mice. AU - Varela,María José, AU - Brea,José, AU - Loza,Maria Isabel, AU - Maldonado,Rafael, AU - Robledo,Patricia, PY - 2011/6/30/entrez PY - 2011/6/30/pubmed PY - 2011/11/16/medline SP - 362 EP - 9 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 22 IS - 4 N2 - The behavioral and neurochemical adaptations related to chronic 3,4-methylenedioxymethamphetamine (MDMA) treatment are largely unknown. In this study, we assessed whether repeated administration of MDMA would induce (a) context-dependent locomotor sensitization in mice and (b) changes in serotonin 5-HT(2A) and dopamine D₂ receptor functionality as measured by [³⁵S]GTPγS binding. Mice were treated with MDMA (10 mg/kg, intraperitoneally) or saline every other day for 11 days either in their home cages or in the environment where locomotor activity was measured. After a 10-day withdrawal period, mice were challenged with MDMA (5 and 10 mg/kg) and saline before locomotor activity measurements. During repeated MDMA treatment, locomotion was progressively enhanced, indicating the development of behavioral sensitization. The MDMA challenge at a dose of 5 mg/kg increased locomotor activity to a greater extent in mice pretreated with MDMA in the testing apparatus than in mice pretreated in the home cages, revealing that contextual cues paired with repeated drug exposure can enhance the expression of behavioral sensitization to MDMA. In contrast, a challenge administration of MDMA at 10 mg/kg induced similar locomotor sensitization in mice pretreated in both environments. An increase in the functionality of cortical 5-HT(2A) receptors was observed in mice pretreated with MDMA compared with mice pretreated with saline, but this activation was significantly greater in mice pretreated in the locomotor environment. In contrast, the functional activity of striatal D₂ receptors was significantly decreased only in mice pretreated with MDMA in the testing apparatus. These results reveal neuroadaptations in cortical 5-HT(2A) and striatal D₂ receptors after MDMA-induced behavioral sensitization in mice. SN - 1473-5849 UR - https://www.unboundmedicine.com/medline/citation/21712712/Sensitization_to_MDMA_locomotor_effects_and_changes_in_the_functionality_of_5_HT_2A__and_D₂_receptors_in_mice_ L2 - http://dx.doi.org/10.1097/FBP.0b013e3283487346 DB - PRIME DP - Unbound Medicine ER -