Effect of cerebral ischemia on dopamine receptors and uptake sites in the gerbil hippocampus

Dopamine D 1 and D 2 receptors and uptake sites were studied in the gerbil hippocampus, parietal cortex and thalamus 1 h to 7 days after 10 min of cerebral ischemia using the occlusion of bilateral common carotid arteries. [ 3H]SCH23390 ([N-methyl- 3H]R[+]-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-7-ol-benzazepine) and [ 3H]mazindol were used as markers of dopamine D 1 receptors and uptake sites, respectively. [ 3H]Nemonapride was used to label dopamine D 2 receptors. No obvious alteration in [ 3H]SCH23390 and [ 3H]mazindol binding was found in the hippocampus up to 48 h after ischemia. These bindings showed a significant reduction in the hippocampus after 7 days of recirculation. In contrast, [ 3H]nemonapride binding was unaffected in the hippocampus during the recirculation periods. The parietal cortex and thalamus also exhibited no significant changes in [ 3H]SCH23390, [ 3H]nemonapride and [ 3H]mazindol binding after ischemia. MAP2 (microtubule-associated protein 2) immunoreactivity was unchanged in all regions up to 48 h after ischemia. Thereafter, a marked loss of MAP2-immunoreactive neurons was observed in the hippocampal CA1 and CA3 neurons 7 days after recirculation. These findings were consistent with histological observations with cresyl violet staining. Our results demonstrate that dopamine D 1 receptors and dopamine uptake sites in the hippocampus are susceptible to cerebral ischemia, whereas dopamine D 2 receptors in this region are particularly resistant. Furthermore, these findings suggest that dopamine transmission may not be major factor in producing ischemic hippocampal damage.