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

Dexmedetomidine inhibits mitochondria damage and apoptosis of enteric glial cells in experimental intestinal ischemia/reperfusion injury via SIRT3-dependent PINK1/HDAC3/p53 pathway

“…According to the kit instructions, intestinal tissues were made into homogenates and quantified using the bicinchoninic acid (BCA) protein assay. Afterwards, the total MDA level and SOD activity in tissue homogenates were calculated [ 34 ].…”

A review on the mitochondrial toxicity of “ecstasy” (3,4-methylenedioxymethamphetamine, MDMA)

“…In agreement, studies have proven that MDMA decreased mitochondrial complex I activity in the brain of mice ( Puerta et al, 2010 , Barros-Miñones et al, 2015 ). In rats it has also been shown that MDMA induced the collapse of ΔΨm and mitochondrial swelling ( Taghizadeh et al, 2016 , Taghizadeh et al, 2020a , Taghizadeh et al, 2020b ). Given that the main source of ATP in the cell is the mitochondrial electron transport chain, the inhibition of one complex and the collapse of ΔΨm can both greatly contribute to the decrease in the generation of ATP.…”

“… ( Feio-Azevedo et al, 2018 ) Male Wistar rats (200 – 250 g) 5 or 10 or 15 mg/kg × 4, every 24 h (intraperitoneal) MDMA-induced impairments to brain mitochondrial function were significantly correlated with the concentrations of both MDMA and its metabolite 3,4-Methylenedioxyamphetamine (MDA) in plasma, cerebrospinal fluid, and brain. ( Taghizadeh et al, 2020a ) Male Wistar rats (200 – 250 g) 0.5 or 1 μg (intrahippocampal infusion) Bucladesine (10 and 100 μM), a membrane-permeable analog of 3′, 5′-cyclic adenosine monophosphate, 5 min after MDMA infusion, attenuated MDMA-induced increase in ROS formation, collapse of ΔΨm, mitochondrial swelling, and outer membrane damage, cytochrome c release and increased ADP/ATP ratio in isolated brain hippocampal mitochondria. ( Taghizadeh et al, 2020b ) ΔΨm, mitochondrial membrane potential.…”

“…This method of scaling does not account for the differences in MDMA metabolism or administration route between humans and rats, but is certainly of great value for an approximate extrapolation. Looking to the studies described in Table 2 , six of them use the 40 mg/kg dose ( Rusyniak et al, 2005 , Alves et al, 2007 , Alves et al, 2009a , Alves et al, 2009b , Taghizadeh et al, 2016 , Taghizadeh et al, 2020a ), and therefore caution must be applied when translating these results to humans. Once again, as mentioned previously, these studies are relevant from a mechanistic point of view and can steer future research using lower doses and more sensitive techniques.…”

Aromatic Bromination Abolishes Deficits in Visuospatial Learning Induced by MDMA (“Ecstasy”) in Rats While Preserving the Ability to Increase LTP in the Prefrontal Cortex

“…In rats, cognitive disruption seems to be associated with alterations at the hippocampal level, possibly because of the alteration of a glutamatergic NMDA-mediated mechanism at the CA1 region [ 15 ]. In addition, repeated MDMA administration at subtoxic doses reduces visuospatial learning in rodents [ 16 , 17 , 18 ]. This evidence differs from other extensive studies that indicate the administration of sub-toxic doses of MDMA seems not to be able to induce cognitive impairment, including visuospatial learning [ 19 ].…”