Unilateral Ibotenic Acid Lesion of the Caudate Putamen Results in D2 Receptor Alterations on the Contralateral Side

Abstract

Dopaminergic projections to the caudate putamen (CPu) involve fibers in the nigrostriatal pathway from the ipsilateral substantia nigra-pars compacta. Postsynaptic receptor populations on cells receiving this information are composed of both D1 and D2 dopamine receptor subtypes. In the present study, unilateral lesions of the CPu, with ibotenic acid, caused a significant reduction in D2 receptor mRNA on the ipsilateral side, as evidenced by in situ hybridization. Similarly, a reduction of D2 receptor binding (as demonstrated with [3H]raclopride) was observed on the lesioned side. As expected, there was no significant change in the D2 receptor binding on the contralateral side. However, a significant increase of D2 receptor mRNA (>100%) was found in the CPu on the contralateral side when compared to sham-lesioned animals. These results indicate that compensatory changes may be occurring on the unlesioned side of the brain. These changes may reflect elevated transcription from DNA to mRNA or decreased translation of the D2 mRNA to protein following unilateral damage in the CPu. The observation of bilateral influence in the striatal dopamine receptor system may be of paramount importance in understanding movement disorders. These findings could influence the interpretation of results obtained in animal models of human disease in which the dopamine receptor system of the basal ganglia is compromised.