Dopamine D2-receptor knockout mice are protected against dopaminergic neurotoxicity induced by methamphetamine or MDMA
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.