Acute and chronic effects of MDMA on molecular mechanisms implicated in memory formation in rat hippocampus: surface expression of CaMKII and NMDA receptor subunits.
S. Moyano, J. Del Río, D. Frechilla
Pharmacology, Biochemistry, and Behavior September 9, 2005 DOI: 10.1016/j.pbb.2005.07.020 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental animal study Peer reviewed |
|---|---|
| Population | Rats (Wistar) treated repeatedly with MDMA |
| Intervention | MDMA |
| Dose | 10 mg/kg twice daily for 4 consecutive days |
| Duration | 4-day treatment, tested 1 week later |
| Measures | Passive avoidance learning, hippocampal 5-HT levels, Western blotting for NMDA receptor subunits, PSD-95, phosphorylated CaMKII, and PP1 |
| Topics | MDMA |
| Keywords | Hippocampus Animals Rats, wistar N-methyl-3,4-methylenedioxyamphetamine Receptors, n-methyl-d-aspartate Blotting, western Avoidance learning Memory Male Calcium-calmodulin-dependent protein kinases |
| Citations | 29 |
| Key findings | Repeated MDMA (10 mg/kg twice daily for 4 days) markedly reduced hippocampal 5-HT one week later but did not affect passive avoidance learning or membrane levels of NMDA receptor subunits, PSD-95, CaMKII, and PP1. A subsequent drug challenge rapidly reduced PSD-95 immunoreactivity and prevented the learning-specific increase in NR1 and phosphorylated CaMKII, suggesting only transient effects on early memory-consolidation molecules that do not depend on endogenous 5-HT. |
Abstract
Acute 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") treatment induces learning deficits in different animal models. In a passive avoidance learning task in rats, previous studies suggested a role for Ca2+/calmodulin-dependent protein kinase II (CaMKII) and N-methyl-D-aspartate (NMDA) receptors in the acute learning impairment. As cognitive deficits by "ecstasy" in humans have been only reported in frequent recreational users, we examined whether a repeated MDMA treatment could induce in rats lasting molecular changes related to memory consolidation of passive avoidance. In rats with a pronounced 5-HT depletion by MDMA, the effect of another drug challenge was also examined. The surface expression in the hippocampus of NMDA receptor subunits, the scaffolding postsynaptic density protein PSD-95, phosphorylated CaMKII and protein phosphatase 1 (PP1) was measured. In rats repeatedly treated with MDMA (10 mg/kg) twice daily for 4 consecutive days, hippocampal 5-HT levels were markedly reduced 1 week later. At this time, neither learning performance was affected nor changes in membrane levels of NMDA receptor subunits, PSD-95, CaMKII and PP1 were found. In these rats, however, another drug challenge produced a rapid reduction in PSD-95 immunoreactivity and prevented the learning-specific increase in the NMDA receptor NR1 subunit and phosphorylated CaMKII. The results show no lasting change in learning-associated molecular events after a neurotoxic MDMA treatment. This drug only produces transient effects on early molecular events involved in memory consolidation, which do not appear to depend on endogenous 5-HT levels.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 10
- Extensive neuroadaptive changes in cortical gene-transcript expressions of the glutamate system in response to repeated intermittent MDMA administration in adolescent rats BMC Neuroscience April 17, 2008
- Cognitive Effects of MDMA in Laboratory Animals: A Systematic Review Focusing on Dose. Pharmacological Reviews July 1, 2019
- Gene expression analysis indicates reduced memory and cognitive functions in the hippocampus and increase in synaptic reorganization in the frontal cortex 3 weeks after MDMA administration in Dark Agouti rats. BMC Genomics August 2, 2018
- Differential effects of MDMA and cocaine on inhibitory avoidance and object recognition tests in rodents. Neurobiology of Learning and Memory December 2017
- Behavioural and Neurochemical Effects of Acute (±) 3,4 methylenedioxymethamphetamine (MDMA) in the Dopamine D1 Receptor Mutant Rat 2016
and 5 more in the library
Cites 6
- 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Journal of Pharmacology and Experimental Therapeutics September 1, 1987
- Memory impairment in abstinent MDMA ("Ecstasy") users Neurology December 1, 1998
- Altered states: the clinical effects of Ecstasy. Pharmacology & Therapeutics April 2003
- Serotonergic deficits and impaired passive-avoidance learning in rats by MDEA: a comparison with MDMA. Pharmacology, Biochemistry, and Behavior February 2000
- 3,4-Methylenedioxymethamphetamine, serotonin and memory. Journal of Pharmacology and Experimental Therapeutics August 1, 1993
and 1 more in the library