Neurotoxicity and persistent cognitive deficits induced by combined MDMA and alcohol exposure in adolescent rats
Vicente Hernández‐rabaza, Graciela Navarro‐mora, Clara Velázquez-sánchez, Antonio Ferragud, Maria Pilar Marín, José Manuel García‐verdugo, Jaime Renau‐piqueras, Juan J. Canales
Addiction Biology October 1, 2010 DOI: 10.1111/j.1369-1600.2010.00259.x (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | Adolescent rats |
| Interventions | cocaine MDMA alcohol |
| Duration | Two weeks after drug treatments |
| Topics | MDMA Neuroplasticity |
| Keywords | Neurotoxicity Dentate gyrus Doublecortin Hippocampal formation Subgranular zone Memory impairment Population Pharmacology Endocrinology |
| Citations | 40 |
| Key points | Adolescent rats exposed to alcohol and MDMA together, but not to either drug alone, showed memory deficits and loss of mature granule neurons in the dentate gyrus, with memory impairment correlated to granule cell depletion. |
Abstract
ABSTRACT Recent trend assessments of drug consumption reveal an increase in the simultaneous use of several drugs at raves, clubs and college settings among youngsters and young adults. We studied in adolescent rats the effects of repeated exposure to cocaine and 3,4‐methylenedioxymethanphetamine (MDMA, ecstasy), given alone or in combination with alcohol, on memory performance, adult hippocampal neurogenesis and neurotoxicity. Rats were trained two weeks after the drug treatments in the radial arm maze. The results showed that only rats exposed to combinations of alcohol and MDMA exhibited significant memory deficits. Alcohol, MDMA and combinations thereof significantly decreased 5‐bromodeoxyuridine labeling in the dentate gyrus (DG), indicating reduced survival of neuronal precursors. None of the treatments altered the length of the dendritic arbors of doublecortin (DCX)‐positive neurons or the number and length of DCX‐negative gaps in the DG. Thus, changes in adult neurogenesis were not causally related to the cognitive alterations induced by the treatments. Only the combination of alcohol and MDMA significantly decreased the population of mature granule neurons in the DG and increased the presence of cluster of differentiation 11b+ reactive microglia in the bordering areas of the subgranular zone. Critically, memory impairment was correlated with granule cell depletion. These observations demonstrate that exposure to alcohol and MDMA during adolescence, at doses that do not provoke apparent cognitive impairment when given separately, causes neurotoxic alterations affecting the DG region as well as persistent memory deficits. The findings highlight the elevated risk associated with the concurrent recreational use of alcohol and MDMA.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 13
- A proof-of-concept investigation into ketamine as a pharmacological treatment for alcohol dependence: study protocol for a randomised controlled trial Trials April 4, 2017
- Cocaine and MDMA Induce Cellular and Molecular Changes in Adult Neurogenic Systems: Functional Implications Pharmaceuticals June 17, 2011
- The effects of acute and repeated adolescent MDMA exposure on behavior, cognition, and the monoamine neurotransmitter systems: A review of human and pre-clinical research Behavioural Brain Research February 10, 2026
- Striatal Iron Deposition in Recreational MDMA (Ecstasy) Users. Biological Psychiatry: Cognitive Neuroscience and Neuroimaging September 2023
- The Acute Toxic and Neurotoxic Effects of 3,4-methylenedioxymethamphetamine are More Pronounced in Adolescent than Adult Mice Behavioural Brain Research December 3, 2019
and 8 more in the library
Cites 8
- Patterns of simultaneous polysubstance use in drug using university students Human Psychopharmacology: Clinical and Experimental June 1, 2006
- 3,4-Methylenedioxymethamphetamine (MDMA) neurotoxicity in rats: a reappraisal of past and present findings Psychopharmacology March 15, 2006
- Drug seeking in response to a priming injection of MDMA in rats: relationship to initial sensitivity to self-administered MDMA and dorsal striatal dopamine The International Journal of Neuropsychopharmacology March 25, 2010
- Ethanol increases the distribution of MDMA to the rat brain: possible implications in the ethanol-induced potentiation of the psychostimulant effects of MDMA The International Journal of Neuropsychopharmacology December 2, 2008
- Non‐linear pharmacokinetics of MDMA (‘ecstasy’) in humans British Journal of Clinical Pharmacology February 1, 2000
and 3 more in the library