Abstract
Rationale
Several studies have suggested the existence of cognitive deficits after repeated or high doses of 3,4-methylenedioxymethamphetamine (MDMA) in humans and experimental animals. However, the extent of the impairments observed in learning or memory tasks remains unclear.
Objective
The objective of this study was to evaluate the effects of different dosing regimens of MDMA on the ability of mice to learn and recall an active avoidance task.
Materials and methods
Animals were treated with MDMA (0, 1, 3, 10 and 30 mg/kg) under four different experimental conditions, and active avoidance acquisition and recall were evaluated. In experiments 1 and 2, MDMA was administered 1 h before different active avoidance training sessions. In experiments 3 and 4, mice received a repeated treatment with MDMA before or after active avoidance training, respectively. Changes in presynaptic striatal dopamine transporter (DAT) binding sites were evaluated at two different time points in animals receiving a high dose of MDMA (30 mg/kg) or saline twice a day over 4 days.
Results
MDMA administered before the active avoidance sessions interfered with the acquisition and the execution of a previously learned task. A repeated treatment with high doses of MDMA administered before training reduced acquisition of active avoidance in mice, while pre-treatment with both high and low doses of MDMA impaired recall of this task. A reduction in DAT binding was observed 4 days but not 23 days after the last MDMA administration.
Conclusions
Acute MDMA modifies the acquisition and execution of active avoidance in mice, while repeated pre-treatment with MDMA impairs acquisition and recall of this task.
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Acknowledgements
The authors would like to thank Alba Vidal for her assistance in the behavioural studies. Dr. Trigo was supported by Instituto de Salud Carlos III “Ayudas para contratos posdoctorales de perfeccionamiento”. This work was supported by FIS grant number 03/0305, Plan Nacional Sobre Drogas 2005, Redes de grupos ISCIII (RTA G03/005), Ministerio de Ciencia y Tecnología (BFU2004–00920/BFI and GEN2003–20651), Genomics, mechanisms and treatment of addiction (GENADDICT) EC-DG RTD-FPVI-Life Sciences and Health-2003-IP (LSHM-CT-2004-05166), New molecules in mood disorders (NEWMOOD) EC-DG RTD-FPVI-Life Sciences and Health-2003-IP (LSHM-CT-2004–503474), Generalitat de Catalunya 2005SGR00131.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00213-008-1147-2
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Trigo, J.M., Cabrero-Castel, A., Berrendero, F. et al. MDMA modifies active avoidance learning and recall in mice. Psychopharmacology 197, 391–400 (2008). https://doi.org/10.1007/s00213-007-1045-z
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DOI: https://doi.org/10.1007/s00213-007-1045-z