Dopamine D3 receptor stimulation promotes the proliferation of cells derived from the post-natal subventricular zone

In the adult mammalian brain, neural stem cells persist in the subventricular zone (SVZ) where dopamine D-3 receptors are expressed. Here, we demonstrate that addition of 1 mum apomorphine increases cell numbers in post-natal SVZ cell cultures. This effect was prevented by a co-treatment with haloperidol, sulpiride or U-99194A, a D-3-preferring antagonist, and mimicked by the dopamine D-3 receptor selective agonist 7-hydroxy-dipropylaminotetralin (7-OH-DPAT). EC50 values were 4.04 +/- 1.54 nm for apomorphine and 0.63 +/- 0.13 nm for 7-OH-DPAT, which fits the pharmacological profile of the D-3 receptor. D-3 receptors were detected in SVZ cells by RT-PCR and immunocytochemistry. D-3 receptors were expressed in numerous beta-III tubulin immunopositive cells. The fraction of apoptotic nuclei remained unchanged following apomorphine treatment, thus ruling out any possible effect on cell survival. In contrast, proliferation was increased as both the proportion of nuclei incorporating bromo-deoxyuridine and the expression of the cell division marker cyclin D-1 were enhanced. These findings provide support for a regulatory role of dopamine over cellular dynamics in post-natal SVZ.