Food-Induced Increase of Acetylcholine in Mouse Hypothalamus

Using microdialysis in C57Bl6 mice, we monitored cholinergic activity in the hypothalamus. Food intake after an overnight fast caused a 3-fold increase of extracellular acetylcholine (ACh) concentrations in the hypothalamus. The effect lasted for about 30 min. Food containing no calories (kaolin pellets), or food that was presented but not accessible, also increased ACh release. In contrast, injections of glucose or β-hydroxybutyrate did not change extracellular ACh. Mice deficient in muscarinic M₃ receptors had the same cholinergic response as wild-type mice. We conclude that the increase of ACh in the hypothalamus was not caused by local detection of nutrients but by anticipation of food intake. This suggests the involvement of motivational circuits in the basal forebrain which is reinforced by the fact that we found slight increases of ACh in the nucleus accumbens during feeding.