Transection of corticostriatal afferents abolishes the hyperexpression of Fos and counteracts the development of rotational overcompensation induced by intrastriatal dopamine-rich grafts when challenged with amphetamine.
The present study was carried out to test whether the abnormally high striatal Fos activation induced by amphetamine and the overcompensation of amphetamine-induced rotation in 6-hydroxydopamine-lesioned rats receiving transplants of fetal nigral neurons can be reduced by a lesion of the corticostriatal projection. Fetal ventral mesencephalic tissue was transplanted as a cell suspension into the dopamine-denervated striatum of unilaterally 6-hydroxydopamine-lesioned rats. Rats in which the transplants had produced a complete compensation or reversal of the lesion-induced rotational asymmetry in response to amphetamine (5 mg/kg, i.p.) were divided into two equal groups, sustaining either a knife-cut transection of prefrontal corticofugal efferents ipsilaterally to the grafts, or a sham-lesion. The animals were re-tested for amphetamine-induced rotation one week post-operatively, and were perfusion-fixed two hours after drug administration. Adjacent sections through the striatum were processed for Fos and tyrosine hydroxylase immunohistochemistry. At the amphetamine rotation test performed after cortical lesion surgery, the frontocortically deafferented animals exhibited a low rate of rotation in the direction ipsilateral to the dopaminergically denervated and grafted side, while sham-lesioned rats rotated towards the intact side. In sham-lesioned controls, the density of Fos-immunoreactive nuclei (no. of nuclei/mm2) was significantly higher in the reinnervated portion of the grafted striatum than on the contralateral side (+54 to 316%). In the frontocortically deafferented-grafted striata, Fos expression was not different from that measured on the contralateral side and significantly lower than in the sham-lesioned controls (-65-79%).(ABSTRACT TRUNCATED AT 250 WORDS)
Cenci
M A
MA
Department of Medical Cell Research, University of Lund, Sweden.
Björklund
A
A
D000344:Afferent Pathways / Q000502:physiology; D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000032:analysis*; D004525:Efferent Pathways / Q000502:physiology; D005260:Female; D016332:Fetal Tissue Transplantation / Q000502:physiology*; D009474:Neurons / Q000637:transplantation; D016627:Oxidopamine; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012399:Rotation; D013378:Substantia Nigra / Q000166:cytology / Q000637:transplantation*
D016760:Proto-Oncogene Proteins c-fos; D016627:Oxidopamine; D000661:Amphetamine; D004298:Dopamine