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

L. A. Ruocco, A. Di Pizzo, U. A. Gironi Carnevale, M. Murolo, A. G. Sadile, C. Arra, E. Topo, A. D'Aniello, A. Curcio, D. Melisi, M. G. Rimoli

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
Pages (from-to)37-44
Number of pages8
JournalBehavioural Brain Research
Volume198
Issue number1
DOIs
Publication statusPublished - Mar 2 2009

Keywords

  • Animal model
  • HPLC
  • Neurogenetics
  • Prodrug

ASJC Scopus subject areas

  • Behavioral Neuroscience

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    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. (2009). 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. Behavioural Brain Research, 198(1), 37-44. https://doi.org/10.1016/j.bbr.2008.11.006