Effect of SA4503 on the electrically evoked release of (3)H-acetylcholine from striatal and hippocampal rat brain slices

Recent microdialysis data has shown that the systemic administration of the selective sigma(1) receptor agonist SA4503 increases the extracellular levels of acetylcholine (ACh) in the hippocampus, but not the striatum, of freely moving rats. In the present study, we examined the effect of SA4503 on the electrically evoked release of (3)H-ACh in rat brain slices isolated from the hippocampus and striatum. At 100 and 300 nM concentrations of SA4503, the electrically evoked release of (3)H-ACh was increased in hippocampal but not striatal slices. Concentrations below 100 nM did not alter the electrically evoked release of (3)H-ACh in either brain area. These results tentatively suggest that the increase in extracellular ACh levels observed in the hippocampus after the systemic administration of SA4503 could in part be related to its interaction with sigma(1) receptors in the hippocampus.