Evidence of an interaction between serotoninergic and cholinergic neurons in the corpus striatum and hippocampus of the rat brain

The existence of an interaction between serotoninergic and cholinergic neurons in the brain has been investigated by studying the effects of quipazine and d-fenfluramine on regional brain acetylcholine in various experimental conditions. Quipazine, at a dose of 10 mg/kg, i.p., significantly increased the levels of acetylcholine in the striatum and hippocampus but not in the telencephalon and brain stem. The striatal increase was not significantly modified by electrolytic lesions placed in the midbrain raphe nuclei, an important site of origin of serotonin-containing neurons in the brain. On the other hand, pretreatment with serotonin antagonists such as methergoline and cinanserin or with parachlorophenylalanine, a serotonin synthesis blocker, prevented the increase of striatal acetylcholine induced by quipazine. Impairment of nigrostriatal dopaminergic mechanisms by local application of 6-hydroxydopamine or by pretreatment with alpha-methylparatyrosine did not modify the effect of quipazine on acetylcholine. The quipazine-induced increase in hippocampal acetylcholine was instead completely blocked by an electrolytic lesion of the nucleus medianus raphe. d-Fenfluramine also significantly increased striatal acetycholine, this effect being completely prevented by parachlorophenylalanine pretreatment. These findings are compatible with the hypothesis that serotoninergic neurons originating in the raphe nuclei may normally serve to inhibit cholinergic neurons in two areas of the rat brain, i.e. the corpus striatum and the hippocampus.