Modulation of hippocampal acetylcholine release after fimbria-fornix lesions and septal transplantation in rats.
Female Long-Evans rats sustained electrolytic lesions of the fimbria and the dorsal fornix causing a partial lesion of the septohippocampal pathway. Two weeks later, the rats received intra-hippocampal grafts of fetal septal cell suspensions. Nine to twelve months later, the release of acetylcholine (ACh) in the hippocampus of sham-operated, lesion-only and grafted rats was measured by microdialysis. The extent of cholinergic (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 compared to sham-operated rats, indicating a loss of endogenous inhibitory mechanisms. Scopolamine (0.5 mg/kg i.p.), a muscarinic antagonist, increased ACh release in all treatment groups. 8-OH-DPAT (0.5 mg/kg s.c.), an agonist at serotonergic 5HT1A-receptors, induced an increase of 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 influence on the grafted cholinergic neurons.
Erb
C
C
Pharmakologisches Institut der Universität Mainz, Germany.
Klein
J
J
Köppen
A
A
Löffelholz
K
K
Jeltsch
H
H
Cassel
J C
JC
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D016380:Brain Tissue Transplantation; D002799:Cholinergic Fibers / Q000737:chemistry / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017551:Microdialysis; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009434:Neural Pathways; D011903:Raphe Nuclei / Q000737:chemistry / Q000166:cytology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000032:analysis; D044263:Receptors, Serotonin, 5-HT1; D012601:Scopolamine / Q000494:pharmacology; D012686:Septal Nuclei / Q000166:cytology / Q000601:surgery*
D018727:Muscarinic Antagonists; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D012601:Scopolamine; D000109:Acetylcholine