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(+/-)-3,4-Methylenedioxymethamphetamine treatment in adult rats impairs path integration learning: a comparison of
Matthew R Skelton1, Jessica A Able, Curtis E Grace
1Division of Neurology, Cincinnati Children's Research Foundation and University of Cincinnati College of Medicine, Cincinnati, OH 45229-3039, USA.
Abstract:
3,4-Methlylenedioxymethamphetamine (MDMA) administration (4 x 15 mg/kg) on a single day has been shown to cause path integration deficits in rats. While most animal experiments focus on single binge-type models of MDMA use, many MDMA users take the drug on a recurring basis. The purpose of this study was to compare the effects of repeated single-day treatments with MDMA (4 x 15 mg/kg) once weekly for 5 weeks to animals that only received MDMA on week 5 and saline on weeks 1-4. In animals treated with MDMA for 5 weeks, there was an increase in time spent in the open area of the elevated zero maze suggesting a decrease in anxiety or increase in impulsivity compared to the animals given MDMA for 1 week and saline treated controls. Regardless of dosing regimen, MDMA treatment produced path integration deficits as evidenced by an increase in latency to find the goal in the Cincinnati water maze. Animals treated with MDMA also showed a transient hypoactivity that was not present when the animals were re-tested at the end of cognitive testing. In addition, both MDMA-treated groups showed comparable hyperactive responses to a later methamphetamine challenge. No differences were observed in spatial learning in the Morris water maze during acquisition or reversal but MDMA-related deficits were seen on reduced platform-size trials. Taken together, the data show that a single-day regimen of MDMA induces deficits similar to that of multiple weekly treatments.
Insights
A single day of 3,4-Methlylenedioxymethamphetamine (MDMA) caused lasting path integration deficits in rats. Recurring MDMA treatments did not worsen these cognitive impairments compared to single-day exposure.
Area of Science:
- Neuroscience
- Behavioral Pharmacology
- Drug Abuse Research
Background:
- Single-day 3,4-Methlylenedioxymethamphetamine (MDMA) administration can impair path integration in rats.
- Most studies use binge-exposure models, but real-world MDMA use is often recurring.
- Understanding the long-term effects of different MDMA dosing regimens is crucial.
Purpose of the Study:
- To compare the neurobehavioral effects of repeated weekly MDMA treatments versus a single-day exposure.
- To investigate potential cumulative effects of MDMA on cognitive functions and anxiety-like behaviors.
- To assess the impact of MDMA dosing on responses to subsequent challenges.
Main Methods:
- Rats received repeated single-day MDMA (4 x 15 mg/kg) weekly for 5 weeks, or MDMA only on week 5.
- Cognitive assessments included the Cincinnati water maze (path integration) and Morris water maze (spatial learning).
- Anxiety-like behavior was measured using the elevated zero maze; locomotor activity and responses to methamphetamine challenge were also recorded.
Main Results:
- Both single-day and repeated MDMA treatments induced path integration deficits.
- Repeated MDMA treatment increased time in the open area of the elevated zero maze, suggesting reduced anxiety or increased impulsivity.
- MDMA caused transient hypoactivity and comparable hyperactive responses to a methamphetamine challenge in both groups.
Conclusions:
- A single day of MDMA administration can induce significant and lasting path integration deficits.
- Repeated weekly MDMA treatments do not necessarily exacerbate these specific cognitive deficits compared to single-day exposure.
- MDMA's effects on anxiety-like behaviors and subsequent stimulant responses warrant further investigation in recurring use models.
