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MDMA modifies active avoidance learning and recall in mice
José Manuel Trigo1, Araceli Cabrero-Castel, Fernando Berrendero
1Laboratori de Neurofarmacologia, Departament de Ciències Experimentals i de la Salut, Universitat Pompeu Fabra, Barcelona, Spain.
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.
Insights
3,4-methylenedioxymethamphetamine (MDMA) impairs learning and memory in mice. Acute MDMA disrupts task acquisition and recall, while repeated high doses reduce learning and memory performance, affecting dopamine transporter binding.
Area of Science:
- Neuroscience
- Pharmacology
- Cognitive Science
Background:
- Studies suggest cognitive deficits following 3,4-methylenedioxymethamphetamine (MDMA) exposure.
- The precise impact of MDMA on learning and memory remains incompletely understood.
Purpose of the Study:
- To investigate the effects of various MDMA dosing regimens on active avoidance learning and recall in mice.
- To assess the impact of MDMA on dopamine transporter (DAT) binding.
Main Methods:
- Mice received acute or repeated MDMA doses (0-30 mg/kg) under different experimental conditions.
- Active avoidance acquisition and recall were evaluated.
- Dopamine transporter (DAT) binding was assessed post-MDMA administration.
Main Results:
- Acute MDMA administration before training impaired active avoidance acquisition and recall.
- Repeated high-dose MDMA before training reduced acquisition, while pre-treatment with high and low doses impaired recall.
- Reduced DAT binding was observed 4 days, but not 23 days, after the last MDMA dose.
Conclusions:
- Acute MDMA administration affects active avoidance learning and performance in mice.
- Repeated MDMA pre-treatment significantly impairs both the acquisition and recall of active avoidance tasks.
- MDMA-induced changes in DAT binding are transient.
