MORPHOLOGICAL AND BIOCHEMICAL ADAPTATIONS TO UNILATERAL DOPAMINE DENERVATION OF THE NEOSTRIATUM IN NEWBORN RATS

Basal ganglia of adult rats a ere examined for morphological and bioch emical changes resulting from neonatal unilateral dopamine denervation of the striatum with increasing doses of 6-hydroxydopamine (4, 12 and 20 mu g). Rotational behaviour induced by apomorphine (0.1 mg/kg) was observed in all rats injected with the high dose (20 mu g) and totall y absent in those injected with the low dose (4 mu g). As assessed wit h tyrosine hydroxylase immunocytochemistry, the extent of dopamine den ervation within the injected striatum was clearly related to the dose injected. In the mesencephalon, losses of tyrosine hydroxylase-immunor eactive cell bodies were proportional to the dose injected and the ext ent of neostriatal dopamine denervation. This retrograde cell loss pre dominated in the ventromedial and lateral parts of the substantia nigr a pars compacta, with relative sparing of the ventral tegmental area. After the injection of the intermediate (12 mu g) and the high (20 mu g) doses, a network of thin tyrosine hydroxylase-immunoreactive fibres was visualized in the ventral part of the pars reticulata ipsilateral to the injected striatum, suggesting a neoinnervation of this structu re by dopamine axons. After the high dose, the density of serotonin-im munoreactive fibers was enhanced in the anterior half of the lesioned striatum. Associated changes in dopamine and serotonin content and tur nover were also documented on both sides, in the striatum and in two o utput structures of the basal ganglia, the globus pallidus and the sub stantia nigra. Dopamine content was decreased only on the injected sid e. After the low dose, equal reductions (-60%) were observed in the an terior striatum and the substantia nigra, whereas a more marked decrea se was measured in the anterior striatum (-93%) than in the substantia nigra (-60% to -74%) after the intermediate and high doses. In the gl obus pallidus, dopamine tissue content was decreased (-51%) only after the high dose. Dopamine turnover was unchanged after the low dose in all structures examined and was increased in the striatum, on the lesi oned side only, after the intermediate and high doses. Serotonin conte nt was increased only on the injected side in the anterior striatum (50% after the low and +92% after the high dose). Serotonin turnover wa s unchanged on the injected side but increased by +118% and by +81% in the contralateral anterior striatum after the low and high doses, res pectively. It was also increased in both substantia nigra after the hi gh dose. In conclusion, morphological changes similar to those describ ed after a bilateral neonatal lesion were observed on the injected sid e in the model of the unilateral neonatal nigrostriatal dopamine dener vation. Biochemical changes were, however, not restricted to the lesio ned side. Notably, changes in serotonin turnover developed on the cont ralateral side. These morphological and biochemical adaptative changes need to be taken into account in considering the mechanisms implicate d in the rotional behaviour measured in these animals. (C) 1997 IBRO. Published by Elsevier Science Ltd.