Effects of cerebral ischemia on regional dopamine release and D1 and D2 receptors

Abstract

To expand on the nature of regional cerebral vulnerability to ischemia, the release of dopamine (DA) and dopaminergic (D1 and D2) receptors were investigated in Mongolian gerbils subjected to bilateral carotid artery occlusion (15 min) alone or with reflow (1-2 h). Extracellular cortical and striatal content of DA and its metabolites was measured by microdialysis using HPLC with electrochemical detection. The kinetic properties of D1 and/or D2 receptor binding sites were determined in cortical and striatal membranes with the use of radiolabeled ligands (125I-SCH23982 and [3H]YM-09151-2, respectively). The ischemic release of DA from the striatum was greater (400-fold over preischemic level) than that from the cortex (12-fold over preischemic content). The affinity for the D1-receptor ligand was lower (KD = 1.248 +/- 0.047 nM) after ischemia than that for sham controls (KD = 0.928 +/- 0.032 nM, p < 0.001). The number of binding sites for D2 receptors decreased in striatum (Bmax = 428 +/- 18.4 fmol/mg of protein) after ischemia compared with sham controls (Bmax = 510 +/- 25.2 fmol/mg of protein, p < 0.05). D1 or D2 binding sites were not changed either in the ischemic cortex or postischemic striatum and cortex. The findings strongly suggest that the ischemic release of DA from striatum is associated with early transient changes in D1- and D2-mediated DA neurotransmission.