Plasticity in serotonin uptake in primary neuronal cultures of serotonin transporter knockout mice

The cross talk between dopaminergic and serotonergic systems in the brain h as multiple neurophysiological and behavioral implications. Primary neurona l cultures of embryonic wild type (+/+) and serotonin transporter knockout (-/-) mice were used as a model to elucidate the possibility of plasticity at the level of serotonin uptake. Serotonergic neurons were identified in m idbrain-hindbrain cultures of both wild type and knockout mice, using polyc lonal anti-serotonin antibodies. Adding serotonin (10 muM) to wild type mid brain-hindbrain cultures increased the intensity of serotonin immunostainin g, but did not change the number of serotonergic neurons. This increased in tensity of serotonin staining was blocked by the serotonin transporter inhi bitors fluoxetine and imipramine, but not with the dopamine transporter inh ibitor nomifensine. In serotonin transporter knockout cultures, however, se rotonin increased both the intensity of serotonin immunostaining and the nu mber of serotonin positive neurons, and nomifensine decreased the number of serotonin-labeled neurons. Uptake of [H-3]serotonin to wild type midbrain- hindbrain cultures was completely blocked by muM fluoxetine, whereas nomife nsine had a very small effect. In contrast, [H-3]serotonin uptake to seroto nin transporter knockout cultures, although very weak, was better inhibited by nomifensine than fluoxetine. The results imply that midbrain-hindbrain neuronal cultures of knockout mice, that do not express serotonin transport ers, acquire the capacity to take up serotonin, apparently via dopamine tra nsporters. (C) 2001 Elsevier Science B.V. All rights reserved.