Regional differences of the effect of sigma receptor ligands on the acetylcholine release in the rat brain.

We found that sigma receptor ligands differentially regulated the acetylcholine (ACh) neurotransmission in the rat brain. Acute administration of (+)-N-allylnormetazocine [(+)-SKF-10,047], a prototype sigma 1 receptor ligand, and 1,3-di(2-tolyl)guanidine (DTG), a non-specific sigma receptor ligand, increased the extracellular ACh level in the rat hippocampus. This increase of hippocampal extracellular ACh level elicited by (+)-SKF-10,047 was more potent than that elicited by DTG. On the other hand, the striatal extracellular ACh level was slightly affected by (+)-SKF-10,047. In addition, DTG did not affect the striatal extracellular ACh level. Our previous studies have shown that both (+)-SKF-10,047 and DTG increased the extracellular ACh level in the rat frontal cortex. Taking all these data into consideration, the regulation of ACh neurotransmission by sigma receptor ligands are different depending upon the brain region.