Abstract
The purpose of the present work was to assess the effects of glufosinate ammonium (GLA), an aminoacid structurally related to glutamate, on in vivo dopamine (DA) release from rat striatum, using brain microdialysis coupled to HPLC-EC. Intrastriatal administration of GLA produced significant concentration-dependent increases in DA levels. At least two mechanisms can be proposed to explain these increases: GLA could be inducing DA release from synaptic vesicles or producing an inhibition of DA transporter (DAT). Thus, we investigated the effects of GLA under Ca++-free condition, and after pretreatment with reserpine and TTX. It was observed that the pretreatment with Ca++-free Ringer, reserpine or TTX significantly reduced the DA release induced by GLA. Coinfusion of GLA and nomifensine shows that the GLA-induced DA release did not involve the DAT. These results show that GLA-induced striatal DA release is probably mediated by an exocytotic-, Ca++-, action potential-dependent mechanism, being independent of DAT.
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Aswad DW (1984) Determination of d- and l-aspartate in amino acid mixtures by high performance liquid chromatography after derivatization with a chiral adduct of o-phthaldialdehyde. Anal Biochem 137:405–407
Bak LK, Schousbo A, Waagepetersen HS (2006) The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J Neurochem 98:641–653
Calas GG, Richard O, Même S, Beloeil JC, Doan BT, Gefflaut T, Même W, Crusio WE, Pichon J, Montécot C (2008) Chronic exposure to glufosinate-ammonium induces spatial memory impairments, hippocampal MRI modifications and glutamine synthetase activation in mice. Neurotoxicology 29:740–747
Cianca RC, Barbosa RD, Faro LR, Adan LV, Gago-Martínez A, Pallares MA (2009) Differential changes of neuroactive amino acids in samples obtained from discrete rat brain regions after systemic administration of saxitoxin. Neurochem Int 54:308–313
David HN, Ansseau M, Abraini JH (2005) Dopamine–glutamate reciprocal modulation of release and motor responses in the rat caudate–putamen and nucleus accumbens of ‘‘intact’’ animals. Brain Res Rev 50:336–360
Durán R, Alfonso M, Arias B (1998) Determination of biogenic amines in rat brain dialysates by high performance liquid chromatography. J Liq Chromatogr Relat Technol 21:2799–2811
Elverfors A, Pileblad E, Lagerkvist S, Bergquist F, Jonason J, Nissbrandt H (1997) 3-Methoxytyramine formation following monoamine oxidase inhibition is a poor index of dendritic DA release in the substantia nigra. J Neurochem 69:1684–1692
Fagg GE, Lanthorn TH (1985) Cl2/Ca21-dependent l-glutamate binding sites do not correspond to 2-amino-4-phosphonobutanoate-sensitive excitatory amino acid receptors. Br J Pharmacol 86:743–751
Gluck MR, Zeevalk GD (2004) Inhibition of brain mitochondrial respiration by dopamine and its metabolites: implications for Parkinson’s disease and catecholamine-associated diseases. J Neurochem 91:788–795
Hack R, Ebert E, Ehling G, Leist KH (1994) Glufosinate ammonium-some aspects of its mode of action in mammals. Food Chem Toxicol 32:461–470
Heeringa MJ, Abercrombie ED (1995) Biochemistry of somatodendritic dopa- mine release in substantia nigra: an in vivo comparison with striatal dopamine release. J Neurochem 65:192–200
Kannari K, Tanaka H, Maeda T, Tomiyama M, Suda T, Matsunaga M (2000) Reserpine pretreatment prevents increases in extracellular striatal dopamine following L-DOPA administration in rats with nigrostriatal denervation. J Neurochem 74:263–269
Lapouble E, Montecot C, Sevestre A, Pichon J (2002) Phosphinothricin induces epileptic activity via nitric oxide production through NMDA receptor activation in adult mice. Brain Res 957:46–52
Lea PJ, Joy KW, Ramo JL, Guerrero MG (1984) The action of 2-amino-4-(methylphosphinyl)-butanoic acid (phosphinothricin) and its 2-oxo-derivative on the metabolism of cyanobacteria and higher plants. Phytochemistry 23:1–6
Leviel V (2001) The reverse transporter of DA, What the physiological significance? Neurochem Int 38:83–106
Logusch EW, Walker DM, McDonald JF, Franz JE (1989) Substrate variability as a factor in enzyme inhibitor design: inhibition of ovine brain glutamine synthetase by alpha- and gamma-substituted phosphinothricins. Biochemistry 28:3043–3051
Matsumura N, Takeuchi C, Hishikawa K, Fujii T, Nakaki T (2001) GLA ammonium induces convulsion through N-methyl-d-aspartate receptors in mice. Neurosci Lett 304:123–125
Meiergerd SM, Schenk JO (1994) Kinetic evaluation of the commonality between the site(s) of action of cocaine and some other structurally similar and dissimilar inhibitors of the striatal transporter for DA. J Neurochem 63:1683–1692
Meme S, Calas AG, Montécot C, Richard O, Gautier H, Gefflaut T, Doan BT, Même W, Pichon J, Beloeil JC (2009) MRI characterization of structural mouse brain changes in response to chronic exposure to the glufosinate ammonium herbicide. Toxicol Sci 111:321–330
Nakaki T, Mishima A, Suzuki E, Shintani F, Fujii T (2000) GLA ammonium stimulates nitric oxide production through N-methyl d-aspartate receptors in rat cerebellum. Neurosci Lett 290:209–212
Park HY, Lee PH, Shin DH, Kim GW (2006) Anterograde amnesia with hippocampal lesions following GLA intoxication. Neurology 67:914–915
Paxinos G, Watson C (1986) The rat brain: in stereotaxic coordinates, 4th edn. Academic Press, New York
Roth JA, Breakefield XO, Castiglione CM (1976) Monoamine oxidase and catechol-O-methyltransferase activities in cultured human skin fibroblasts. Life Sci 19:1705–1710
Tanaka J, Yamashita M, Yamashita M, Matsuo H, Yamamoto T (1998) Two cases of GLA poisoning with late onset convulsions. Vet Hum Toxicol 40:219–222
Tarazi FI, Baldessarini RJ (1999) Regional localization of dopamine and ionotropic glutamate receptor subtypes in striatolimbic brain regions. J Neurosci Res 55:401–410
Tarazi FI, Campbell A, Yeghiayan SK, Baldessarini RJ (1998) Localization of ionotropic glutamate receptors in caudate–putamen and nucleus accumbens septi of rat brain: comparison of NMDA, AMPA, and kainate receptors. Synapse 30:227–235
Tolwani RJ, Jakowec MW, Petzinger GM, Green S, Waggie K (1999) Experimental models of Parkinson’s disease: insights from many models. Lab Anim Sci 49:363–371
Watanabe T, Sano T (1998) Neurological effects of GLA poisoning with a brief review. Hum Exp Toxicol 17:35–39
Wendler C, Wild A (1990) Effect of phosphinothricin (Glufosinate) on photosynthesis and photorespiration. Z Naturforsch 45:535–537
Wieczorek WJ, Kruk ZL (1994) A quantitative comparison on the effects of benztropine, cocaine and nomifensine on electrically evoked DA overflow and rate of re-uptake in the caudate putamen and nucleus accumbens in the rat brain slice. Brain Res 657:42–50
Wood PL, Altar CA (1988) Dopamine release in vivo from nigrostriatal, mesolimbic, and mesocortical neurons: utility of 3-methoxytyramine measurements. Pharmacol Rev 40:163–187
Zetterström T, Brundin P, Gage FH, Sharp T, Isacson O, Dunnett SB, Ungerstedt U, Björklund A (1986) In vivo measurement of spontaneous release and metabolism of dopamine from intrastriatal nigral grafts using intracerebral dialysis. Brain Res 362:344–349
Acknowledgments
Brenda Nunes acknowledges MAEC-AECID (Spain) for a research grant. The research was supported by grant (Contract-Program) from University of Vigo (0022 122F641.02).
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Ferreira Nunes, B.V., Durán, R., Alfonso, M. et al. Evaluation of the effects and mechanisms of action of glufosinate, an organophosphate insecticide, on striatal dopamine release by using in vivo microdialysis in freely moving rats. Arch Toxicol 84, 777–785 (2010). https://doi.org/10.1007/s00204-010-0533-9
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DOI: https://doi.org/10.1007/s00204-010-0533-9