| First Author | Fumagalli F | Year | 1998 |
| Journal | J Neurosci | Volume | 18 |
| Issue | 13 | Pages | 4861-9 |
| PubMed ID | 9634552 | Mgi Jnum | J:48189 |
| Mgi Id | MGI:1266924 | Doi | 10.1523/JNEUROSCI.18-13-04861.1998 |
| Citation | Fumagalli F, et al. (1998) Role of dopamine transporter in methamphetamine-induced neurotoxicity: evidence from mice lacking the transporter. J Neurosci 18(13):4861-9 |
| abstractText | The role of the dopamine transporter (DAT) in mediating the neurotoxic effects of meth-amphetamine (METH) was tested in mice lacking DAT. Dopamine (DA) and serotonin (5-HT) content, glial fibrillary acidic protein (GFAP) expression, and free radical formation were assessed as markers of METH neurotoxicity in the striatum and/or hippocampus of wild-type, heterozygote, and homozygote (DAT -/-) mice. Four injections of METH (15 mg/kg, s.c.), each given 2 hr apart, produced 80 and 30% decreases in striatal DA and 5-HT levels, respectively, in wild-type animals 2 d after administration. In addition, GFAP mRNA and protein expression levels, extracellular DA levels, and free radical formation were increased markedly. Hippocampal 5-HT content was decreased significantly as well (43%). Conversely, no significant changes were observed in total DA content, GFAP expression, extracellular DA levels, or free radical formation in the striatum of DAT -/- mice after METH administration. However, modest decreases were observed in striatal and hippocampal 5-HT levels (10 and 17%, respectively). These observations demonstrate that DAT is required for, and DA is an essential mediator of, METH-induced striatal dopaminergic neurotoxicity, whereas serotonergic deficits are only partially dependent on DAT. |
