Differential Response of nNOS Knockout Mice to MDMA (“Ecstasy”)‐ and Methamphetamine‐Induced Psychomotor Sensitization and Neurotoxicity
Annals of the New York Academy of Sciences October 1, 2004 Yossef Itzhak, Karen L. Anderson, Syed F. Ali 31 citations
Mice lacking the neuronal nitric oxide synthase (nNOS) gene are resistant to methamphetamine-induced psychomotor sensitization and dopaminergic neurotoxicity, but not to serotonin-mediated effects of MDMA (Ecstasy). Repeated MDMA administration caused psychomotor sensitization in both normal and nNOS knockout mice, while methamphetamine caused sensitization only in normal mice. Sensitization to both drugs persisted for 40 days in normal mice but not in knockouts. High-dose MDMA depleted serotonin in several brain regions of both types, indicating nNOS absence does not protect against serotonin loss. Striatal dopamine neurotoxicity from high-dose MDMA and methamphetamine was partially prevented in knockouts given MDMA and fully prevented in knockouts given methamphetamine. The nNOS gene is required for dopamine-mediated effects of both drugs but not for serotonin-mediated effects of MDMA.