title: Mediation of glutamatergic receptors and nitric oxide on striatal dopamine release evoked by anatoxin-a. An in vivo microdialysis study.
abstract: In this work, the involvement of ionotropic glutamatergic receptors and nitric oxide on striatal dopamine release induced by anatoxin-a was investigated in conscious and freely-moving rats. To study the participation of glutamatergic receptors, the effects of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptors antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and N-methyl-D-aspartate (NMDA) receptor antagonists, dizocilpine (MK-801) and d(-)-2-amino-5-phosphonopentanoic acid (APV), were examined. The perfusion of 3.5 mM anatoxin-a increased the extracellular dopamine levels to 701% relative to the basal. When CNQX was administered with 3.5 mM anatoxin-a, the increase of dopamine levels was 29% smaller than that observed with anatoxin-a alone. When MK-801 and APV were administered, the effect of anatoxin-a was attenuated 26% and 25% respectively in terms of that observed with anatoxin-a alone. And with CNQX plus MK-801, the effect of anatoxin-a was 53% inhibited in terms of the effect of anatoxin-a alone. These results suggest that the striatal dopamine release induced by anatoxin-a is partly mediated by activation of both ionotropic glutamatergic receptors. Since the neuronal form of nitric oxide synthase (nNOS) produces nitric oxide (NO) primarily in response to activation of NMDA receptors, it was tested if NO could play any role in the effect of anatoxin-a. Treatment with NOS inhibitors, L-nitro-arginine methyl ester (L-NAME) and d(-)-2-amino-5-phosphonopentanoic acid (7-NI), induced decreased anatoxin-a effects of 22% and 26% respectively. In conclusion, the present in vivo results demonstrate that anatoxin-a induced an indirect activation of ionotropic glutamatergic receptors (NMDA and AMPA/kainite receptors), which stimulate striatal dopamine release. On the other hand, activation of NMDA receptors may elicit NO increased levels enhancing dopamine release.
authors.affiliation: Department of Functional Biology and Health Sciences, Faculty of Biology, University of Vigo, Vigo (Pontevedra), Spain. fcampos@uvigo.es
authors.forename: Francisco
authors.initials: F
authors.lastname: Campos
authors.forename: Miguel
authors.initials: M
authors.lastname: Alfonso
authors.forename: Lucia
authors.initials: L
authors.lastname: Vidal
authors.forename: Lilian R F
authors.initials: LR
authors.lastname: Faro
authors.forename: Rafael
authors.initials: R
authors.lastname: Durán
mesh_terms: D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism*; D000087522:Cyanobacteria Toxins; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D007191:Indazoles / Q000494:pharmacology; D052998:Microcystins / Q000633:toxicity*; D017551:Microdialysis; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors / Q000378:metabolism; D018092:Kainic Acid Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D014326:Tropanes
chemical_list: D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D000087522:Cyanobacteria Toxins; D016291:Dizocilpine Maleate; D004298:Dopamine; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D007191:Indazoles; D052998:Microcystins; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate; D014326:Tropanes; C509783:anatoxin a; C080122:7-nitroindazole