Open AccessNeuroprotective Effects of the MAO ‐ B Inhibitor, PF 9601 N , in an In Vivo Model of Excitotoxicity
Author(s) -
Bolea Irene,
Colivicchi Maria Alessandra,
Ballini Chiara,
MarcoContelles José,
Tipton Keith Francis,
Unzeta Mercedes,
Della Corte Laura
Publication year - 2014
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12271
Subject(s) - excitotoxicity , neuroprotection , pharmacology , microdialysis , in vivo , ex vivo , chemistry , kainate receptor , glutamate receptor , kainic acid , biochemistry , in vitro , medicine , biology , extracellular , ampa receptor , receptor , microbiology and biotechnology
Summary Background PF 9601 N [ N ‐(2‐propynyl)‐2‐(5‐benzyloxy‐indolyl) methylamine] is an inhibitor of monoamine oxidase B ( MAO ‐ B ), which has shown to possess neuroprotective properties in several in vitro and in vivo models of P arkinson's disease ( PD ). As there is evidence that excitotoxicity may be implicated in the pathophysiology of several neurodegenerative diseases, the aim of the present work was to investigate the effects of PF 9601 N in an acute in vivo model of excitotoxicity induced by the local administration of kainic acid during striatal microdialysis in adult rats. Methods The basal and evoked release of neurotransmitters was monitored by HPLC analysis of microdialysate samples and tissue damage was evaluated histologically “ ex vivo .” Results PF 9601 N (40 mg/kg, single i.p. administration) reduced the kainate‐evoked release of glutamate and aspartate and increased taurine release, but it had no effect on the release of dopamine, DOPAC , and HVA . PF 9601 N pretreatment also resulted in a significant reduction in the kainate‐induced astrocytosis, microgliosis, and apoptosis. Conclusions The results suggest PF 9601 N to be a good candidate for the treatment of neurodegenerative diseases mediated by excitotoxicity.