MDMA modifies active avoidance learning and recall in mice.
BACKGROUND
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.


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.
Trigo
José Manuel
JM
Laboratori de Neurofarmacologia, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
Cabrero-Castel
Araceli
A
Berrendero
Fernando
F
Maldonado
Rafael
R
Robledo
Patricia
P
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D000818:Animals; D001245:Association Learning / Q000187:drug effects; D001362:Avoidance Learning / Q000187:drug effects*; D003214:Conditioning, Classical / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005239:Fear / Q000187:drug effects; D008297:Male; D011939:Mental Recall / Q000187:drug effects*; D051379:Mice; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D012153:Retention, Psychology / Q000187:drug effects
D018759:Adrenergic Uptake Inhibitors; D050483:Dopamine Plasma Membrane Transport Proteins; D018817:N-Methyl-3,4-methylenedioxyamphetamine