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Increased anxiety and impaired memory in rats 3 months after administration of 3,4-methylenedioxymethamphetamine
K C Morley1, J E Gallate, G E Hunt
1Department of Psychology, University of Sydney, Sydney, NSW 2006, Australia.
Abstract:
Male Wistar rats were administered either (a) a high dose regime of 3,4-methylenedioxymethamphetamine (MDMA) (4 x 5 mg/kg, i.p. over 4 h on each of 2 consecutive days), (b) a moderate dose regime of MDMA (1 x 5 mg/kg on each of 2 consecutive days), (c) D-amphetamine (4 x 1 mg/kg over 4 h on each of 2 days), or (d) vehicle injections. The high MDMA dose regime and the amphetamine treatment both produced acute hyperactivity and hyperthermia. Twelve weeks later, all rats were tested in the drug-free state on a battery of anxiety tests (elevated plus maze, emergence and social interaction tests). A further 2 weeks later they were tested on a novel object recognition memory task. Rats previously given the neurotoxic dose of MDMA showed greater anxiety-like behaviour on all three anxiety tests relative to both controls and D-amphetamine-treated rats. Rats given the moderate MDMA dose regime also showed increased anxiety-like behaviour on all three tests, although to a lesser extent than rats in the high dose group. In the object recognition task, rats given the high MDMA dose regime showed impaired memory relative to all other groups when tested at a 15-min delay but not at a 60-min delay. Rats previously exposed to amphetamine did not differ from saline controls in the anxiety or memory tests. These data suggest that moderate to heavy MDMA exposure over 48 h may lead to increased anxiety and memory impairment 3 months later, possibly through a neurotoxic effect on brain serotonin systems.
Insights
High and moderate doses of 3,4-methylenedioxymethamphetamine (MDMA) caused long-term anxiety in rats. MDMA exposure also led to memory impairment, suggesting potential neurotoxic effects on serotonin systems.
Area of Science:
- Neuroscience
- Psychopharmacology
- Toxicology
Background:
- 3,4-methylenedioxymethamphetamine (MDMA) is a recreational drug with known acute effects.
- Long-term consequences of MDMA exposure, particularly on anxiety and memory, require further investigation.
- Serotonin system neurotoxicity is a potential mechanism underlying MDMA's delayed effects.
Purpose of the Study:
- To investigate the long-term effects of different 3,4-methylenedioxymethamphetamine (MDMA) dosage regimens on anxiety-like behavior and memory in rats.
- To compare the effects of MDMA with D-amphetamine, a related stimulant, on these behavioral outcomes.
- To explore potential neurotoxic mechanisms, specifically involving serotonin systems, underlying observed behavioral changes.
Main Methods:
- Male Wistar rats received high-dose MDMA, moderate-dose MDMA, D-amphetamine, or vehicle injections over two consecutive days.
- Twelve weeks post-treatment, rats were assessed for anxiety-like behavior using elevated plus maze, emergence, and social interaction tests.
- Two weeks later, a novel object recognition task was administered to evaluate memory function.
Main Results:
- High-dose MDMA treatment resulted in significantly increased anxiety-like behavior across all tests compared to controls and D-amphetamine-treated rats.
- Moderate-dose MDMA also induced greater anxiety-like behavior, though less pronounced than the high-dose group.
- Rats receiving high-dose MDMA exhibited impaired memory in the novel object recognition task at a 15-min delay, but not at a 60-min delay. D-amphetamine exposure did not alter anxiety or memory performance.
- Amphetamine-treated rats did not differ from saline controls in anxiety or memory tests.
Conclusions:
- Moderate to high-dose MDMA exposure over 48 hours can lead to persistent increases in anxiety-like behavior and memory deficits approximately three months later.
- These long-term behavioral changes may be mediated by neurotoxic effects on brain serotonin systems induced by MDMA.
- D-amphetamine, at the tested doses, did not produce similar long-term anxiety or memory impairments, suggesting differential neurotoxic potential compared to MDMA.
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