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

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 D1 and D2 receptors were examined using autoradiography while changes in D2 receptor 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 D1 receptors was not affected by the lesion while D2 receptors density was increased by 20-25% in the more rostral part of the neostriatum. Changes in D2 MRNA after the lesion paralleled those observed for D2 receptor density, i.e. D2 mRNA level was increased by 15-19% in the rostral neostriatum. The graft did not influence D1 receptor densities but reversed the post-lesion increase of D2 receptors associated parameters. It is concluded that dopaminergic grafts implanted in neonatal hosts are able to normalise the density of D2 receptors by an action on their synthesis. © 1995.