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Intermittent ethanol exposure increases long-lasting behavioral and neurochemical effects of MDMA in adolescent mice

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Abstract

Rationale

Heavy binge drinking is increasingly frequent among adolescents, while ethanol (EtOH) is often used in combination with 3,4-methylenedioxymethamphetamine (MDMA).

Objectives

The long-lasting effects of intermittent exposure to EtOH and MDMA during adolescence on motor activity, anxiety, and social behavior were evaluated in adult mice. The concentration of brain monoamines in the striatum, cortex, and hippocampus was measured following the behavioral test.

Methods

Adolescent OF1 mice were exposed to ethanol (1.25 g/kg) on two consecutive days at 48-h intervals over a 14-day period (from PND 29 to 42). A total of eight injections of MDMA (10 or 20 mg/kg) were administered twice daily at 4-h intervals over two consecutive days, and this schedule was repeated 6 days later (PND 33, 34, 41, and 42). Behavioral tests and analysis of brain monoamines took place on PND 64 to 67.

Results

Exposure to MDMA during adolescence increased the anxiogenic response in the elevated plus maze, with adult mice spending less time in the open arms of the maze and exhibiting lower concentrations of DA in the striatum. A pattern of ethanol administration modeling binge drinking during adolescence enhanced these effects and undermined the hyperthermic response induced by MDMA. Passive avoidance was affected only when EtOH was administered alone.

Conclusions

Juvenile administration of MDMA and alcohol was found to cause a decrease in monoamine levels in adulthood, as well as changes in social interaction behaviors, locomotor activity, increase measures of anxiety in the elevated plus maze (EPM), and decrease step-through latencies in passive avoidance test.

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Acknowledgements

We wish to thank Mr. Brian Normanly for his editing of the manuscript. This work was supported by the following grants: Ministerio de Ciencia e Innovación. Dirección General de Investigación (PSI2008-00101/PSIC), Instituto de Salud “Carlos III” (FIS), RETICS, Red de Trastornos Adictivos (RD06/001/0016 and 0019) and Generalitat Valenciana, Conselleria de Educación (PROMETEO/2009/072), Spain.

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Authors and Affiliations

  1. Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de Valencia, Avda. Blasco Ibáñez 21, 46010, Valencia, Spain

    Marta Rodríguez-Arias, Concepción Maldonado, Antonio Vidal-Infer, María A. Aguilar & José Miñarro

  2. Department of Cellular Pathology, Centro de Investigación Príncipe Felipe, Avda. Autopista del Saler, 16, 46013, Valencia, Spain

    Consuelo Guerri

Authors
  1. Marta Rodríguez-Arias
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  2. Concepción Maldonado
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  3. Antonio Vidal-Infer
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  4. Consuelo Guerri
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  5. María A. Aguilar
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  6. José Miñarro
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Corresponding author

Correspondence to Marta Rodríguez-Arias.

Additional information

The experimental protocol has been approved by an Institutional Review Committee for the use of animal subjects. Procedures involving mice and their care were conducted in conformity with national, regional, and local laws and regulations, which are in accordance with European Community Council Directives (86/609/EEC, 24 November 1986).

The authors have no possible conflict of interest in the carrying out and reporting of this research.

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Rodríguez-Arias, M., Maldonado, C., Vidal-Infer, A. et al. Intermittent ethanol exposure increases long-lasting behavioral and neurochemical effects of MDMA in adolescent mice. Psychopharmacology 218, 429–442 (2011). https://doi.org/10.1007/s00213-011-2329-x

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  • DOI: https://doi.org/10.1007/s00213-011-2329-x

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