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Dose concentration and spatial memory and brain mitochondrial function association after
G Taghizadeh1, H Mehdizadeh2, H Lavasani3
1Rehabilitation Research Center, Department of Occupational Therapy, School of Rehabilitation Sciences, Iran University of Medical Sciences, Tehran, Iran.
Abstract:
MDMA-induced impairments of memory performance have been reported in different human and animal studies. However, the correlation between spatial memory impairment, brain mitochondrial function, and concentrations of MDMA and its metabolites has not yet been investigated despite it being needed for comparison with human studies. Therefore, the aim of this study was to investigate the dose concentration and spatial memory as well as brain mitochondrial function association after MDMA administration in rats. We assessed the effects of MDMA [0.5, 2.5, 5, 10 and 15 mg/kg; intraperitoneally (I.P)] on spatial memory of male Wistar rats in the Morris water maze test (MWM) and brain mitochondrial function (i.e., reactive oxygen species, mitochondrial membrane potential, swelling and outer membrane damage, cytochrome c release, and ADP/ATP ratio). Concentrations of MDMA and its metabolite, MDA, were determined in plasma, cerebrospinal fluid (CSF) and brain which was obtained immediately after probe test of MWM (i.e., 4 h after last training trial). The results of this study indicate nonlinear kinetics of MDMA after I.P adminstration. Also, an insignificant correlation was observed between MDMA doses and the MDA/MDMA ratio in plasma, CSF, and brain. Moreover, the results showed that MDMA, but not MDA, accumulated in brain tissue by increasing the administered doses. Beside, MDMA-induced impairments of spatial memory and brain mitochondrial function were significantly correlated with the concentrations of both MDMA and MDA in plasma, CSF, and brain. Therefore, it can be suggested that MDMA and its metabolite, MDA, affect spatial memory and brain mitochondrial function.
Insights
MDMA impairs spatial memory and brain mitochondrial function in rats. These impairments correlate with MDMA and its metabolite MDA levels in the brain and bodily fluids.
Area of Science:
- Neuroscience
- Pharmacology
- Toxicology
Background:
- MDMA (3,4-methylenedioxymethamphetamine) use is linked to memory deficits.
- The relationship between MDMA, its metabolite MDA, spatial memory, and brain mitochondrial function remains understudied in animal models.
Purpose of the Study:
- To investigate the dose-dependent effects of MDMA on spatial memory and brain mitochondrial function in rats.
- To determine the correlation between MDMA and MDA concentrations in plasma, CSF, and brain with observed impairments.
Main Methods:
- Rats received varying intraperitoneal doses of MDMA (0.5-15 mg/kg).
- Spatial memory was assessed using the Morris water maze (MWM) test.
- Brain mitochondrial function was evaluated through measures of reactive oxygen species, membrane potential, swelling, outer membrane damage, cytochrome c release, and ADP/ATP ratio.
Main Results:
- MDMA exhibited nonlinear kinetics and dose-dependent accumulation in brain tissue.
- Spatial memory and mitochondrial function were impaired in a manner correlated with MDMA and MDA concentrations.
- No significant correlation was found between MDMA doses and the MDA/MDMA ratio.
Conclusions:
- MDMA administration leads to dose-dependent spatial memory deficits and compromised brain mitochondrial function in rats.
- Both MDMA and its metabolite MDA contribute to these neurotoxic effects.
- Findings suggest a direct link between MDMA/MDA levels and cognitive/mitochondrial dysfunction.
