SEROTONIN AXONS OF THE NEOSTRIATUM SHOW A HIGHER AFFINITY FOR STRIATAL THAN FOR VENTRAL MESENCEPHALIC TRANSPLANTS - A QUANTITATIVE STUDY INADULT AND IMMATURE RECIPIENT RATS

We previously showed that grafts of fetal ventral mesencephalic tissue are practically not innervated by host serotonin (5-HT) axons after i mplantation into the striatum of rats aged more than 14 days, at varia nce with transplants of cortical or striatal tissue into the adult str iatum, which are well innervated by these axons. Using 5-HT immunohist ochemistry and in vitro [H-3]5-HT uptake/autoradiography, we have exam ined and quantified the innervation of ventral mesencephalic versus st riatal grafts several months after implantation into the striatum of n eonatal (postnatal day 5 or P5), juvenile (P15), and adult rats. Ventr al mesencephalic grafts implanted in P5 rats received a moderate 5-HT innervation, while similar grafts implanted in P15 or adult recipients were almost free of any 5-HT fibers (-80%, compared to P5). The densi ty of 5-HT innervation showed a tendency toward higher values in stria tal than in ventral mesencephalic grafts (1.6-2 times higher in P5 and adult recipients; 4 times higher in P15 recipients). The difference w as more striking, and significant, when only the true striatal portion s of the striatal grafts were considered, i.e., DARPP-32-immunopositiv e areas (4-5 times higher in P5 and adult recipients; 10 times higher in P15 recipients). Accordingly, these DARPP-32-positive areas were al so more densely innervated than the DARPP-32-negative zones of the sam e grafts (3 times higher at any age). The 5-HT innervation density als o decreased with increasing age of the recipients in DARPP-32-positive , as well as DARPP-32-negative compartments of the striatal grafts (-7 5% in adults), but this decrease appeared more gradual (-50% in juveni les) than with mesencephalic grafts. It is concluded that the 5-HT axo ns innervating the neostriatum have a better affinity for striatal gra fts than for ventral mesencephalic grafts or the nonstriatal portions of striatal grafts. In adulthood, the relative affinity of these axons for the different types of grafts is maintained, even though their gr owth capacity decreases irrespective of the target tissue considered. This experimental model may prove useful for the identification of the receptors and ligands that are responsible for target recognition by 5-HT axons and to test the possibility that the progressive decrease o f axonal growth capacity from neonatal age to adulthood be related to a downregulation of such molecules. (C) 1998 Academic Press.