title: Angiotensin IV and LVV-haemorphin 7 enhance spatial working memory in rats: effects on hippocampal glucose levels and blood flow.
abstract: The IRAP ligands Angiotensin IV (Ang IV) and LVV-haemorphin 7 (LVV-H7) enhance performance in a range of memory paradigms in normal rats and ameliorate memory deficits in rat models for amnesia. The mechanism by which these peptides facilitate memory remains to be elucidated. In recent in vitro experiments, we demonstrated that Ang IV and LVV-H7 potentiate activity-evoked glucose uptake into hippocampal neurons. This raises the possibility that IRAP ligands may facilitate memory in hippocampus-dependent tasks through enhancement of hippocampal glucose uptake. Acute intracerebroventricular (i.c.v.) administration of 1nmol Ang IV or 0.1nmol LVV-H7 in 3 months-old Sprague-Dawley rats enhanced spatial working memory in the plus maze spontaneous alternation task. Extracellular hippocampal glucose levels were monitored before, during and after behavioral testing using in vivo microdialysis. Extracellular hippocampal glucose levels decreased significantly to about 70% of baseline when the animals explored the plus maze, but remained constant when the animals were placed into a novel control chamber. Ang IV and LVV-H7 did not significantly alter hippocampal glucose levels compared to control animals in the plus maze or control chamber. Both peptides had no effect on hippocampal blood flow as determined by laser Doppler flowmetry, excluding that either peptide increased the hippocampal supply of glucose. We demonstrated for the first time that Ang IV and LVV-H7 enhance spatial working memory in the plus maze spontaneous alternation task but no in vivo evidence was found for enhanced hippocampal glucose uptake or blood flow.
authors.affiliation: Research Group Experimental Pharmacology, Department of Pharmaceutical Chemistry, Drug Analysis and Drug Information, Vrije Universiteit Brussel, Brussels, Belgium.
authors.forename: Dimitri
authors.initials: D
authors.lastname: De Bundel
authors.forename: Ilse
authors.initials: I
authors.lastname: Smolders
authors.forename: Rui
authors.initials: R
authors.lastname: Yang
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Albiston
authors.forename: Yvette
authors.initials: Y
authors.lastname: Michotte
authors.forename: Siew Yeen
authors.initials: SY
authors.lastname: Chai
mesh_terms: D000804:Angiotensin II / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002404:Catheterization; D002560:Cerebrovascular Circulation / Q000187:drug effects; D005110:Extracellular Space / Q000378:metabolism; D045268:Flowmeters; D005947:Glucose / Q000378:metabolism; D006454:Hemoglobins / Q000494:pharmacology*; D006624:Hippocampus / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects* / Q000502:physiology; D017551:Microdialysis; D009043:Motor Activity / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013028:Space Perception / Q000187:drug effects* / Q000502:physiology; D013037:Spatial Behavior / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D006454:Hemoglobins; D010446:Peptide Fragments; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C012877:angiotensin II, des-Asp(1)-des-Arg(2)-Ile(5)-; C074309:LVV-hemorphin-7; D005947:Glucose