title: Intrastriatal dopamine-rich implants reverse the changes in dopamine D2 receptor densities caused by 6-hydroxydopamine lesion of the nigrostriatal pathway in rats: an autoradiographic study.
abstract: The aim of the present study was to test whether intrastriatal implants of embryonic dopaminergic neurons are able to normalize the lesion-induced hypersensitivity of striatal dopaminergic receptors. The ascending dopaminergic pathway of adult rats was unilaterally lesioned using 6-hydroxydopamine. Three weeks later a cell suspension obtained from the mesencephali of ED 14 rat embryos was implanted into the denervated striatum. Rotational responses to dopaminergic agonists were tested five months after implantation. One month later animals were killed and striatal dopaminergic receptor densities were quantified using autoradiography, the dopaminergic reinnervation of the host striatum being visualized with [3H]GBR 12935, a ligand labelling dopamine uptake sites. The lesion induced a behavioural hypersensitivity to dopaminergic agonists and lesioned animals displayed a strong rotation contralateral to the lesion in response to a test dose of the D1 agonist compound SKF 38393 (2.5 mg/kg) or of the D2 agonist LY 171555 (0.15 mg/kg). These responses were completely abolished by the graft. The normal distribution of D1 and D2 dopaminergic receptors in the rat striatum was similar to that described previously. Seven months after the lesion of the nigrostriatal dopaminergic pathway, the density of D1 receptors was not significantly affected while the density of D2 receptors was increased by about 25-50%. The implantation of embryonic dopaminergic neurons into the denervated striatum led to a slight decrease of D1 receptor densities and to a reversal of the lesion-induced increase of striatal dopaminergic D2 receptors six months later. Moreover, this reversal concerned not only the reinnervated striatal region but also extended into non-reinnervated areas of the striatum. It is concluded that grafts of embryonic dopaminergic neurons can normalize the density of dopaminergic D2 receptors.
authors.affiliation: INSERM U.318, LAPSEN, CHU de Grenoble, France.
authors.forename: M
authors.initials: M
authors.lastname: Savasta
authors.forename: F
authors.initials: F
authors.lastname: Mennicken
authors.forename: M
authors.initials: M
authors.lastname: Chritin
authors.forename: D N
authors.initials: DN
authors.lastname: Abrous
authors.forename: C
authors.initials: C
authors.lastname: Feuerstein
authors.forename: M
authors.initials: M
authors.lastname: Le Moal
authors.forename: J P
authors.initials: JP
authors.lastname: Herman
mesh_terms: D000818:Animals; D001345:Autoradiography; D001552:Benzazepines / Q000494:pharmacology; D016380:Brain Tissue Transplantation / Q000502:physiology; D003342:Corpus Striatum / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000008:administration & dosage / Q000494:pharmacology*; D018492:Dopamine Antagonists; D005260:Female; D008297:Male; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D016627:Oxidopamine / Q000633:toxicity*; D011247:Pregnancy; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects* / Q000378:metabolism; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012399:Rotation; D012457:Salicylamides / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000187:drug effects / Q000502:physiology*
chemical_list: D001552:Benzazepines; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D020891:Raclopride; D016627:Oxidopamine; D004298:Dopamine