Development of striatal dopaminergic function .3. Pre- and postnatal development of striatal and cortical mRNAs for the neurotrophin receptors trkB(TK+) and trkC and their regulation by synaptic dopamine

Known neurotrophins in the nigrostriatal system include brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) which exert biological effects after high affinity binding to their respective tyrosine kinase receptors, trkB and trkC. We measured striatal trkB(TK+) and trkC mRNAs in rat brain sections with in situ hybridization histochemistry. Both trkB(TK+) and trkC transcripts were present in the striatal anlage at embryonic day (E) 14 or 16. Striatal trkB(TK+) mRNA levels increased to a peak in the late prenatal period and gradually declined in the postnatal period. In contrast, striatal trkC mRNA levels peaked on E16, then declined to fairly constant levels. Striatal trkB(TK+) gene expression increased from the medial to lateral quadrants throughout development, whereas trkC mRNA increased from the lateral to medial quadrants prenatally but increased from the dorsal to ventral quadrants on postnatal days (P) 1 and 3. The distinct spatiotemporal developmental profiles of trkB(TK+) and trkC mRNA suggest that their respective ligands BDNF and NT-4/5, and NT-3, may have specialized functions in striatal neuronal development. Because neurotransmitters may regulate neurotrophin function in developing neural systems, we treated rats of various ages with the indirect dopamine agonist cocaine and measured the effects of cocaine treatment on transcription of the trk genes. Acute 1 h cocaine treatment increased trkB(TK+) and trkC mRNA levels in the P5 striatum but not in the E15, E20, or adult striatum. The trkB(TK+) effect was blocked by pretreatment with the D1 receptor antagonist, SCH23390, and was not affected by pretreatment with the D2 receptor antagonist, eticlopride. In contrast, trkC regulation may be mediated by independent stimulation of D1 and D2 receptors. We hypothesize that the endogenous nigrostriatal neurotransmitter dopamine can modulate striatal neurotrophin responsiveness and thereby influence striatal neuronal development during a defined developmental period.