MDMA Pretreatment Leads to Mild Chronic Unpredictable Stress-Induced Impairments in Spatial Learning

Jacobi I. Cunningham, Jamie Raudensky, John Tonkiss, Bryan K. Yamamoto

Research output: Contribution to journalArticle

19 Scopus citations


3,4-Methylenedioxymethamphetamine (MDMA) is a drug of abuse worldwide and a selective serotonin (5-HT) neurotoxin. An important factor in the risk of drug abuse and relapse is stress. Although multiple parallels exist between MDMA abuse and stress, including effects on 5-HTergic neurotransmission, few studies have investigated the consequences of combined exposure to MDMA and chronic stress. Therefore, rats were pretreated with MDMA and exposed 7 days later to 10 days of mild chronic unpredictable stress (CUS). MDMA pretreatment was hypothesized to enhance the effects of CUS leading to enhanced 5-HT transporter (SERT) depletion in the hippocampus and increased anxiety and cognitive impairment. Whereas MDMA alone increased anxiety-like behavior on the elevated plus maze, CUS alone or in combination with MDMA pretreatment did not increase anxiety-like behavior. In contrast, MDMA pretreatment led to CUS-induced learning impairment in the Morris water maze but not an enhanced depletion of hippocampal SERT protein. These results show that prior exposure to MDMA leads to stress-induced impairments in learning behavior that is not otherwise observed with stress alone and appear unrelated to an enhanced depletion of SERT.

Original languageEnglish (US)
Pages (from-to)1076-1084
Number of pages9
JournalBehavioral Neuroscience
Issue number5
StatePublished - Oct 2009


  • MDMA
  • Morris water maze
  • chronic unpredictable stress
  • elevated plus maze
  • hippocampus

ASJC Scopus subject areas

  • Behavioral Neuroscience

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