MDMA enhances hippocampal-dependent learning and memory under restrictive conditions, and modifies hippocampal spine density
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Addictive drugs produce forms of structural plasticity in the nucleus accumbens and prefrontal cortex. The aim of this study was to investigate the impact of chronic MDMA exposure on pyramidal neurons in the CA1 region of hippocampus and drug-related spatial learning and memory changes.
Methods and results
Adolescent rats were exposed to saline or MDMA in a regime that mimicked chronic administration. One week later, when acquisition or reference memory was evaluated in a standard Morris water maze (MWM), no differences were obtained between groups. However, MDMA-exposed animals performed better when the MWM was implemented under more difficult conditions. Animals of MDMA group were less anxious and were more prepared to take risks, as in the open field test they ventured more frequently into the central area. We have demonstrated that MDMA caused an increase in brain-derived neurotrophic factor (BDNF) expression. When spine density was evaluated, MDMA-treated rats presented a reduced density when compared with saline, but overall, training increased the total number of spines, concluding that in MDMA-group, training prevented a reduction in spine density or induced its recovery.
This study provides support for the conclusion that binge administration of MDMA, known to be associated to neurotoxic damage of hippocampal serotonergic terminals, increases BDNF expression and stimulates synaptic plasticity when associated with training. In these conditions, adolescent rats perform better in a more difficult water maze task under restricted conditions of learning and memory. The effect on this task could be modulated by other behavioural changes provoked by MDMA.
KeywordsAdolescent rats Brain-derived neurotrophic factor Hippocampus Learning MDMA Spines
The authors acknowledge the Language Advisory Service of the University of Barcelona for revising the language of the manuscript. S. Abad is a fellow of Institut de Biomedicina (IBUB, University of Barcelona). This work was supported by grants from Spanish Ministerio de Ciencia e Innovación (SAF2010-15948, SAF2011-23631 and SAF2012-39852-C02-01) and from the Generalitat de Catalunya (SGR0977).
Conflict of Interest
The authors have no financial or non-financial competing interests in relation to the work described here.
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