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-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.
Ruocco
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LA
Department of Experimental Medicine, Second University of Naples, Via S. Andrea delle Dame, 7, 80138 Naples, Italy. luciaadriana.ruocco@unina2.it
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Murolo
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Sadile
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D'Aniello
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D000818:Animals; D001224:Aspartic Acid / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001288:Attention / Q000187:drug effects; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D001522:Behavior, Animal / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D018846:Excitatory Amino Acids / Q000378:metabolism*; D005106:Exploratory Behavior / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007279:Injections, Subcutaneous; D018782:Maze Learning / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D017397:Prefrontal Cortex / Q000378:metabolism; D011355:Prodrugs / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013028:Space Perception / Q000187:drug effects; D016896:Treatment Outcome
D018846:Excitatory Amino Acids; D011355:Prodrugs; C539428:aspartic acid diethyl ester; D001224:Aspartic Acid; D018698:Glutamic Acid