Dose concentration and spatial memory and brain mitochondrial function association after 3,4-methylenedioxymethamphetamine (MDMA) administration in rats

• Published in: Archives of toxicology 2020-03, Vol.94 (3), p.911-925
• Main Authors: Taghizadeh, G., Mehdizadeh, H., Lavasani, H., Hosseinzadeh Ardakani, Y., Foroumadi, A., Halvaei Khankahdani, Z., Moshtagh, A., Pourahmad, J., Sharifzadeh, M., Rouini, M. R.
• Format: Article
• Language: English
• Subjects: Adenosine diphosphate; Animal behavior; Animal memory; Animals; Bioaccumulation; Biomedical and Life Sciences; Biomedicine; Brain; Cerebrospinal fluid; Cognition; Cognitive ability; Correlation analysis; Cytochrome; Cytochrome c; Cytochromes; Cytochromes c; Dose-Response Relationship, Drug; Ecstasy; Environmental Health; Hallucinogens - toxicity; Humans; Male; Maze Learning; MDMA; Membrane potential; Membrane Potential, Mitochondrial; Membranes; Memory Disorders; Memory tasks; Metabolites; Mitochondria; N-Methyl-3,4-methylenedioxyamphetamine - toxicity; Occupational Medicine/Industrial Medicine; Organ Toxicity and Mechanisms; Pharmacology/Toxicology; Rats; Rats, Wistar; Reaction kinetics; Reactive Oxygen Species; Rodents; Serotonin; Spatial analysis; Spatial memory; Spatial Memory - drug effects
• ISSN: 0340-5761; 1432-0738
• DOI: 10.1007/s00204-020-02673-x

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.