In utero exposure to dexamethasone causes a persistent and age-dependent exacerbation of the neurotoxic effects and glia activation induced by MDMA in dopaminergic brain regions of C57BL/6J mice

Withania somnifera influences MDMA-induced hyperthermic, cognitive, neurotoxic and neuroinflammatory effects in mice

“…To further characterize the interplay between WSE and the noxious effects of MDMA in the nigrostriatal system, we also evaluated astroglia and microglial activation. In agreement with our earlier reports [30,40], MDMA increased the number of GFAP-positive cells in the striatum, but not in the SNc. Interestingly, the MDMA-induced increase in striatal GFAP immunoreactivity was not observed in WSE plus MDMA-treated…”

“…MDMA was synthesized, solubilized, and administered by the i.p. route in a volume of 10 ml/kg, as described elsewhere [27,30,40]. The doses of WSE and MDMA were both selected on the basis of our previous studies [8,21,23,27,30,40].…”

“…Prolonged exposure to drugs of abuse such amphetamine and the amphetamine-related drug (+/-)-3,4-methylendioxymethamphetamine (MDMA; "Ecstasy") may induce oxidative stress, mitochondrial dysfunctions, neurodegeneration, and neuroinflammation [25][26][27][28][29][30][31][32][33] in several brain areas that are typically associated with cognitive and memory deficits [20,34]. A limited number of studies have evaluated the possible beneficial influence of WS on the neurotoxic and neuroinflammatory effects elicited by amphetamine-related drugs.…”

“…In this regard, MDMA is an intriguing amphetaminerelated drug to be used as model to assess the neuroprotective properties of WS. Indeed, MDMA has abuse properties and, when administered to mice, it exerts central and peripheral toxic effects that include acute hyperthermia [31,33,36], memory impairment, neurotoxicity, and glial activation in the dopaminergic nigrostriatal and mesolimbic systems [26][27][28][29][30]36]; all these effects could possibly be modulated by WS.…”

“…On these bases, the present study evaluated the potential beneficial effects of WSE on MDMA-induced central toxicity. To this end, we used a previously validated schedule of MDMA treatment [27,30,31] where WSE was co-administered with MDMA and given as pretreatment before WSE and MDMA co-administration. In the SNc and striatum, we evaluated the presence of degeneration of dopaminergic neurons and fibers and of astrogliosis and microgliosis.…”