Neurobiology of Disease
March 22, 2021
Noelia Granado, Sara Ares-Santos, Idaira Oliva et al.
117 citations
The dopamine D2 receptor is necessary for the neurotoxic effects of methamphetamine and MDMA (ecstasy) in mice. In wild-type mice, both drugs caused hyperthermia, loss of dopamine markers (tyrosine hydroxylase and dopamine transporter) in the striatum, inflammation, and dopaminergic cell death in the substantia nigra pars compacta. In mice lacking the D2 receptor (D2R−/−), all these effects were blocked, including the loss of dopaminergic neurons. The neuroprotective effect of D2R inactivation was not solely due to preventing hyperthermia, as reserpine lowered body temperature in both genotypes but potentiated toxicity only in wild-type mice. These results indicate that D2R is essential for methamphetamine and MDMA neurotoxicity, independent of body temperature.
Journal of Neurochemistry
September 24, 2008
Noelia Granado, Esther O’shea, Jordi Bové et al.
112 citations
Repeated doses of MDMA (ecstasy) given to mice cause a lasting loss of dopamine-producing neurons in the substantia nigra, a brain region critical for movement. One day after injection, the number of these neurons drops and remains low for at least 30 days. In the striatum, markers of dopamine function also fall sharply within a day and stay reduced for a month, though some recovery begins after three days, with new nerve fiber growth. Damage is selective: the nucleus accumbens is unaffected, showing MDMA destroys the nigrostriatal pathway but spares the mesolimbic pathway. Immune cell activation follows the same pattern, confirming the link between inflammation and dopamine cell death.
Synapse
October 25, 2007
Noelia Granado, Isabel Escobedo, Esther O’shea et al.
59 citations
The drug MDMA (Ecstasy) damages dopamine nerve terminals in the mouse striatum, with a greater effect in striosomes—specialized brain compartments linked to different functions—than in the surrounding matrix. Mice given MDMA showed significant reductions in two markers of dopamine neurons, tyrosine hydroxylase and dopamine transporter, compared with controls. The loss was considerably more pronounced in striosomes, indicating that these compartments are more vulnerable to MDMA's long-term neurotoxicity. This provides the first evidence that striosome and matrix compartments differ in their sensitivity to MDMA, with the damage primarily involving striosomal dopamine fibers.