MODULATION OF HIPPOCAMPAL ACETYLCHOLINE-RELEASE AFTER FIMBRIA-FORNIX LESIONS AND SEPTAL TRANSPLANTATION IN RATS

Female Long-Evans rats sustained electrolytic lesions of the fimbria a nd the dorsal fornix causing a partial lesion of the septohippocampal pathway. Two weeks later, the rats received intra-hippocampal grafts o f fetal septal cell suspensions. Nine to twelve months later, the rele ase of acetylcholine (ACh) in the hippocampus of sham-operated, lesion -only and grafted rats was measured by microdialysis. The extent of ch olinergic (re)innervation was determined by acetylcholinesterase (AChE ) staining and densitometry. In both lesion-only and grafted rats, the ratio of ACh release to AChE staining intensity was increased as comp ared to sham-operated rats, indicating a loss of endogenous inhibitory mechanisms. Scopolamine (0.5 mg/kg i.p.), a muscarinic antagonist, in creased ACh release in all treatment groups. 8-OH-DPAT (0.5 mg/kg s.c. ), an agonist at serotonergic 5HT(1A)-receptors, induced an increase o f hippocampal ACh release in sham-operated rats. This effect was lost in lesion-only rats, but was fully restored by neuronal grafting. As 8 -OH-DPAT influences hippocampal ACh release by a postsynaptic action, this finding indicates that the host brain exerts a serotonergic influ ence on the grafted cholinergic neurons. (C) 1997 Elsevier Science Ire land Ltd.