| First Author | Mössner R | Year | 2006 |
| Journal | Neurosci Lett | Volume | 401 |
| Issue | 1-2 | Pages | 49-54 |
| PubMed ID | 16638624 | Mgi Jnum | J:144910 |
| Mgi Id | MGI:3832161 | Doi | 10.1016/j.neulet.2006.02.081 |
| Citation | Mossner R, et al. (2006) Aberrant accumulation of serotonin in dopaminergic neurons. Neurosci Lett 401(1-2):49-54 |
| abstractText | Gene targeting approaches greatly facilitate insight into the functioning of monoamine transporters, the targets of potent antidepressants. The serotonin transporter (5-HTT) is the molecular target of a large number of antidepressants. To assess the clearance of serotonin (5-HT) in the absence of the 5-HTT, we have generated double knockout mice lacking both the 5-HTT and the catabolizing enzyme monoamine oxidase A (MAOA). We found aberrant 5-HT accumulation in the striatum of these MAOA/5-HTT double knockout mice. By additional ablation of the dopamine transporter (DAT), this aberrant 5-HT accumulation was abolished in MAOA/5-HTT/DAT triple knockout mice. Thus, aberrant uptake of 5-HT occurs in dopaminergic terminals under conditions of elevated 5-HT levels, and this aberrant uptake is mediated by the DAT. These findings have important consequences for antidepressant therapy, since during treatment of depression with selective serotonin reuptake inhibitors, clearance of 5-HT by dopaminergic neurons may reduce the desired therapeutic elevation of extracellular 5-HT levels. This provides a molecular rationale for improving antidepressant efficacy by additional pharmacological inhibition of the DAT. |
