Serotonergic modulation of hippocampal acetylcholine release after long-term neuronal grafting

Abstract

Adult female rats sustained aspirative fimbria-fornix lesions and, 2 weeks later, received intrahippocampal grafts of fetal septal or mixed septal-raphe cell suspensions. Twenty-four months later, the extracellular concentration of hippocampal acetylcholine (ACh) was determined by microdialysis. Basal ACh levels (5–65 fmol/5 μl in sham-operated rats) were strongly reduced after lesioning (3–7 fmol/5 μl). In septally transplanted and septal-raphe co-transplanted rats, hippocampal ACh concentrations were restored to near-normal levels (15–25 fmol/5 μl), indicating long-term functional survival of hippocampal transplants. After administration of citalopram (100 μM by infusion) and fenfluramine (20 mg/kg i.p.), the hippocampal ACh efflux was increased by 2- to 3-fold in all groups of rats. The relative increase of ACh was highest in cotransplanted rats, an effect which was possibly due to functional interactions between grafted raphe and septal neurons.