Excitatory amino acids in the forebrain of the Naples high-excitability rats: neurochemical and behavioural effects of subchronic d-aspartate and its diethyl ester prodrug

The excitatory amino acids (EAA) l-glutamate ( l-Glu), l-aspartate ( l-Asp) and d-aspartate ( d-Asp) are thought to play a neurotransmitter/neuromodulator role in neuronal communications. Recently, a high level of EAA l-Glu, d- and l-Asp isomers has been found in the forebrain of Naples high-excitab...

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Published in:	Behavioural brain research Vol. 198; no. 1; pp. 37 - 44
Main Authors:	Ruocco, L.A., Di Pizzo, A., Gironi Carnevale, U.A., Murolo, M., Sadile, A.G., Arra, C., Topo, E., D’Aniello, A., Curcio, A., Melisi, D., Rimoli, M.G.
Format:	Journal Article
Language:	English
Published:	Shannon Elsevier B.V 02-03-2009 Elsevier
Subjects:	Animal model Animals Aspartic Acid - administration & dosage Aspartic Acid - analogs & derivatives Aspartic Acid - pharmacology Attention - drug effects Attention Deficit Disorder with Hyperactivity - drug therapy Attention Deficit Disorder with Hyperactivity - metabolism Attention Deficit Disorder with Hyperactivity - physiopathology Behavior, Animal - drug effects Behavioral psychophysiology Biological and medical sciences Chromatography, High Pressure Liquid Corpus Striatum - metabolism Disease Models, Animal Emotions - drug effects Emotions - physiology Excitatory Amino Acids - metabolism Exploratory Behavior - drug effects Fundamental and applied biological sciences. Psychology Glutamic Acid - metabolism Hippocampus - metabolism HPLC Hypothalamus - metabolism Injections, Subcutaneous Maze Learning - drug effects Motor Activity - drug effects Neurogenetics Prefrontal Cortex - metabolism Prodrug Prodrugs - administration & dosage Prodrugs - metabolism Prodrugs - pharmacology Prosencephalon - drug effects Prosencephalon - metabolism Psychology. Psychoanalysis. Psychiatry Psychology. Psychophysiology Rats Rats, Inbred Strains Space Perception - drug effects Treatment Outcome Animal model Prodrug Neurogenetics HPLC Subchronic Rat Rodentia Central nervous system HPLC chromatography Excitability Aspartate Prosencephalon Ester Vertebrata Mammalia Animal Neurotransmitter Excitatory aminoacid Behavior
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Summary:	The excitatory amino acids (EAA) l-glutamate ( l-Glu), l-aspartate ( l-Asp) and d-aspartate ( d-Asp) are thought to play a neurotransmitter/neuromodulator role in neuronal communications. Recently, a high level of EAA l-Glu, d- and l-Asp isomers has been found in the forebrain of Naples high-excitability (NHE) rat line that models the mesocortical variant of Attention-Deficit Hyperactivity Disorder (ADHD). The aim of this study was to assess the functions of d-Asp using two forms, i.e. free d-Asp or d-Asp diethyl ester (DEE) as prodrug, on brain and behaviour. Thus, prepuberal rats were given, for two weeks daily, an i.p. injection of d-Asp or DEE or vehicle. Then rats were exposed to two spatial novelties i.e. Làt and radial Olton maze. Behaviour was monitored for indices of activity, non-selective attention (NSA), selective spatial attention (SSA) and emotional reactivity. l-Glu and d- and l-Asp were detected by HPLC in cognitive and non-cognitive brain areas such as prefrontal cortex, striatum, hippocampus and hypothalamus. Results indicate that subchronic d-Asp or DEE (i) reduced EAA levels in the NHE and increased it in the random-bred controls (NRB) rats, (ii) in the Làt-maze d-Asp increased horizontal activity in NHE but DEE decreased it in NRB rats, (iii) in the Olton maze d-Asp and DEE decreased vertical activity in NHE and NRB rats respectively, (iv) d-Asp impaired attention only in NRB decreasing number of arms visited before first repetition. Therefore, data demonstrate differential effects of prepuberal subchronic d-Asp and DEE that may be related to different basal EAA levels in NHE and NRB rats.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0166-4328 1872-7549
DOI:	10.1016/j.bbr.2008.11.006