title: Decreased striatal dopamine release underlies increased expression of long-term synaptic potentiation at corticostriatal synapses 24 h after 3-nitropropionic-acid-induced chemical hypoxia.
abstract: The striatum is particularly sensitive to the irreversible inhibitor of succinate dehydrogenase 3-nitropropionic acid (3-NP). In the present study, we examined early changes in behavior and dopamine and glutamate synaptic physiology created by a single systemic injection of 3-NP in Fischer 344 rats. Hindlimb dystonia was seen 2 h after 3-NP injections, and rats performed poorly on balance beam and rotarod motor tests 24 h later. Systemic 3-NP increased NMDA receptor-dependent long-term potentiation (LTP) at corticostriatal synapses over the same time period. The 3-NP-induced corticostriatal LTP was not attributable to increased NMDA receptor number or function, because 3-NP did not change MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine] binding or NMDA/AMPA receptor current ratios. The LTP seen 24 h after 3-NP was D(1) receptor dependent and reversed by exogenous addition of dopamine or a D(2) receptor agonist to brain slices. HPLC and fast-scan cyclic voltammetry revealed a decrease in dopamine content and release in rats injected 24 h earlier with 3-NP, and much like the enhanced LTP, dopamine changes were reversed by 48 h. Tyrosine hydroxylase expression was not changed, and there was no evidence of striatal cell loss at 24-48 h after 3-NP exposure. Sprague Dawley rats showed similar physiological responses to systemic 3-NP, albeit with reduced sensitivity. Thus, 3-NP causes significant changes in motor behavior marked by parallel changes in striatal dopamine release and corticostriatal synaptic plasticity.
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, California 90089, USA.
authors.forename: Garnik
authors.initials: G
authors.lastname: Akopian
authors.forename: Cynthia
authors.initials: C
authors.lastname: Crawford
authors.forename: M Flint
authors.initials: MF
authors.lastname: Beal
authors.forename: Maurand
authors.initials: M
authors.lastname: Cappelletti
authors.forename: Michael W
authors.initials: MW
authors.lastname: Jakowec
authors.forename: Giselle M
authors.initials: GM
authors.lastname: Petzinger
authors.forename: Ling
authors.initials: L
authors.lastname: Zheng
authors.forename: Stacey L
authors.initials: SL
authors.lastname: Gheorghe
authors.forename: Carmela M
authors.initials: CM
authors.lastname: Reichel
authors.forename: Robert
authors.initials: R
authors.lastname: Chow
authors.forename: John P
authors.initials: JP
authors.lastname: Walsh
mesh_terms: D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003292:Convulsants / Q000633:toxicity; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D002534:Hypoxia, Brain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D009068:Movement / Q000187:drug effects / Q000502:physiology; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D009498:Neurotoxins / Q000633:toxicity; D009574:Nitro Compounds / Q000633:toxicity; D011422:Propionates / Q000633:toxicity; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013045:Species Specificity; D009435:Synaptic Transmission / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D003292:Convulsants; D018491:Dopamine Agonists; D009498:Neurotoxins; D009574:Nitro Compounds; D011422:Propionates; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C015392:3-nitropropionic acid; D004298:Dopamine
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