Absence of the dopamine D2 receptor leads to a decreased expression of GDNF and NT-4 mRNAs in restricted brain areas

Neurotrophic factors (NTFs) control the metabolic and electrophysiological properties of dopaminergic neurons in the brain, At the level of the substa ntia nigra, NTFs have been proposed to control dopamine release by regulati ng the firing rate of dopaminergic cells. This function is normally control led by presynaptic dopaminergic autoreceptors. Dopamine has also been propo sed to regulate the expression of NTFs and their receptors in the nigrostri atal pathway. Thus, an interaction between the signalling cascades activate d by NTFs and dopamine receptors might possibly influence the physiology of dopaminergic neurons. Among dopamine receptors, D2 receptors (D2R) are the most abundant on dopaminergic neurons, where they exert autoreceptor funct ions. To test for an interaction between the NTF and dopaminergic pathways we have analysed the expression of NTFs and their receptors in D2R-deficien t (D2R -/-) mice. Our study shows that the mRNA levels of brain-derived neu rotrophic factor (BDNF), neurotrophin-3 and their corresponding receptors a re not modified in the dopaminergic system of D2R -/- adult mice compared w ith wild-type littermates. However, a marked reduction of glial cell line-d erived neurotrophic factor (GDNF) and neurotrophin-4 (NT-4) mRNAs is observ ed in the striatum and parietal cortex of D2R -/- mice, respectively. These results implicate dopamine, acting through D2 receptors, in the local cont rol of specific NTF expression. The down-regulation of GDNF and NT-4 expres sion might also contribute to the locomotor phenotype of D2R -/- mice.