The neonatal lesion of the meso-telencephalic dopaminergic pathway increases intrastriatal D2 receptor levels and synthesis and this effect is reversed by neonatal dopaminergic rich-graft

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Abstract

The ascending dopaminergic pathway of 3-day-old rats has been unilaterally destroyed by the injection of 6-hydroxydopamine into the lateral hypothalamus. Five days later, a suspension containing embryonic dopaminergic neurones was injected in the lesioned neostriatum. Rotational responses to dopaminergic agonists were tested eight months after grafting and animals were killed one month later. Neostriatal dopaminergic D1and D2receptors were examined using autoradiography while changes in D2receptor mRNA levels were studied by in situ hybridization. The lesion induced a behavioural hypersensitivity - as manifested in contralateral rotations - to dopaminergic D1(SKF 38393) or D2(LY 171555) agonists which was abolished by the graft. Density of D1receptors was not affected by the lesion while D2receptors density was increased by 20-25% in the more rostral part of the neostriatum. Changes in D2MRNA after the lesion paralleled those observed for D2receptor density, i.e. D2mRNA level was increased by 15-19% in the rostral neostriatum. The graft did not influence D1receptor densities but reversed the post-lesion increase of D2receptors associated parameters. It is concluded that dopaminergic grafts implanted in neonatal hosts are able to normalise the density of D2receptors by an action on their synthesis. © 1995.

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Mennicken, F., Savasta, M., Chritin, M., Feuerstein, C., Le Moal, M., Herman, J. P., & Abrous, D. N. (1995). The neonatal lesion of the meso-telencephalic dopaminergic pathway increases intrastriatal D2 receptor levels and synthesis and this effect is reversed by neonatal dopaminergic rich-graft. Molecular Brain Research, 28(2), 211–221. https://doi.org/10.1016/0169-328X(94)00210-6

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