title: Effect of fimbria-fornix lesion on 125I-angiotensin IV (Ang IV) binding in the guinea pig hippocampus.
abstract: Central administration of angiotensin IV (Ang IV) and its analogues facilitates memory retention and retrieval in normal animals and reverses amnesia induced by scopolamine or by bilateral perforant pathway lesions. Ang IV binds with high affinity and specificity to a novel binding site designated the AT(4) receptor. AT(4) receptors are abundant in the medial septum and hippocampus, a cholinergic pathway associated with memory processing. The aim of this study was to determine whether AT(4) receptors in the guinea pig hippocampus were associated with the neural input from the basal forebrain. The fimbria-fornix was lesioned by a unilateral-knife cut and the brain was processed for 125I-Ang IV binding, acetylcholinesterase, and cresyl violet staining. Unilateral lesions of the fimbria-fornix significantly reduced acetylcholinesterase staining in the ipsilateral hippocampus. The loss in cholinergic input to the hippocampus was associated with a small, but significant, reduction in 125I-Ang IV binding in the CA2 (-9%; P=0.001), and CA3 (-5%; P=0.003) of the rostral hippocampus. No other changes in 125I-Ang IV binding were observed. These results provide evidence that the majority of AT(4) receptor binding occurs in a post-synaptic locus in the guinea pig hippocampus.
authors.affiliation: Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Victoria 3010, Parkville, Australia.
authors.forename: Joohyung
authors.initials: J
authors.lastname: Lee
authors.forename: Siew Yeen
authors.initials: SY
authors.lastname: Chai
authors.forename: Margaret J
authors.initials: MJ
authors.lastname: Morris
authors.forename: Frederick A O
authors.initials: FA
authors.lastname: Mendelsohn
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Allen
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism; D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000378:metabolism*; D000818:Animals; D048588:Benzoxazines; D020712:Fornix, Brain / Q000601:surgery*; D007839:Functional Laterality; D006168:Guinea Pigs; D006624:Hippocampus / Q000378:metabolism*; D007457:Iodine Radioisotopes; D008297:Male; D010078:Oxazines; D011945:Receptors, Angiotensin / Q000378:metabolism*
chemical_list: C090830:AT4 receptor; D048588:Benzoxazines; D007457:Iodine Radioisotopes; D010078:Oxazines; D011945:Receptors, Angiotensin; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; C028911:cresyl violet; D000110:Acetylcholinesterase