Changes in [3H]AMPA and [3H]kainate binding in rat caudate-putamen and nucleus accumbens after 6-hydroxydopamine lesions of the medial forebrain bundle : an autoradiographic study

Abstract The binding parameters of [ 3 H]α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and [ 3 H]kainate binding were examined in caudate-putamen and nucleus accumbens of rat striatum after unilateral lesions of the right medial forebrain bundle (MFB) using in vitro receptor autoradiography. Lesioning of the dopaminergic fibres in the MFB with 6-hydroxydopamine (6-OHDA) resulted, after one or four weeks, in a significant decrease in the levels of [ 3 H]GBR 12935 (1-[2-diphenylmethoxy)-ethyl]-4-(3-phenylpropyl) piperazine) in ipsilateral caudate-putamen and nucleus accumbens (62 and 43%, respectively). A comparison of the dissociation constants ( K d ) of [ 3 H]AMPA and [ 3 H]kainate binding in caudate-putamen and nucleus accumbens between control and MFB-lesioned side did not indicate any significant change. However, the maximum number of [ 3 H]AMPA and [ 3 H]kainate binding sites ( B max ) were significantly decreased in caudate-putamen and nucleus accumbens of the MFB-lesioned side of the brain. This decrease was between 17 and 26%. Our results suggested that at least one-fourth to one-fifth of AMPA and kainate receptors in rat caudate-putamen and nucleus accumbens are localized on the presynaptic endings of dopamine fibres that follow the MFB. A role of non-NMDA glutamate receptors in the presynaptic regulation of dopamine release in rat striatum in therefore supported.