Involvement of NMDA receptors and L-arginine-nitric oxide pathway in the antidepressant-like effects of zinc in mice.
This study investigated the involvement of NMDA receptors and the L-arginine-nitric oxide (NO) pathway in the antidepressant-like effects of zinc in the forced swimming test (FST). The immobility times in the FST and in the tail suspension test (TST) were reduced by zinc chloride (ZnCl(2), 30 and 10-30 mg/kg intraperitoneal (i.p.), respectively). The doses active in the FST and TST reduced locomotor activity in an open-field. The antidepressant-like effect of ZnCl(2) in the FST was prevented by pre-treatment of animals with guanosine 5'-monophosphate (GMP), ascorbic acid, L-arginine, or S-nitroso-N-acetyl-penicillamine (SNAP), but not with D-arginine, administered at doses that per se produced no anti-immobility effect. The immobility time of mice treated with ZnCl(2)+MK-801 was not different from the result obtained with ZnCl(2) or MK-801 alone, but ZnCl(2)+imipramine had a greater effect in the FST than administration of either drug alone. Pre-treatment of animals with a sub-threshold dose of ZnCl(2) prevented the anti-immobility effect of MK-801, ketamine, GMP, L-arginine or N(G)-nitro-L-arginine (L-NNA), but did not alter the effect of imipramine or fluoxetine. Taken together, the results demonstrate that zinc produced an antidepressant-like effect that seems to be mediated through its interaction with NMDA receptors and the L-arginine-NO pathway.
Rosa
Angelo Oscar
AO
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis 88040-900, SC, Brazil.
Lin
Jaime
J
Calixto
João Batista
JB
Santos
Adair Roberto S
AR
Rodrigues
Ana Lúcia S
AL
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001120:Arginine / Q000378:metabolism*; D001205:Ascorbic Acid / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects; D002712:Chlorides / Q000494:pharmacology* / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006157:Guanosine Monophosphate / Q000494:pharmacology; D019417:Hindlimb Suspension / Q000502:physiology; D007099:Imipramine / Q000494:pharmacology; D007103:Immobilization / Q000502:physiology; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D013550:Swimming; D013997:Time Factors; D017967:Zinc Compounds / Q000494:pharmacology* / Q000627:therapeutic use
D000928:Antidepressive Agents; D002712:Chlorides; D004338:Drug Combinations; D018691:Excitatory Amino Acid Antagonists; D016166:Free Radical Scavengers; D020030:Nitric Oxide Donors; D016194:Receptors, N-Methyl-D-Aspartate; D017967:Zinc Compounds; D005473:Fluoxetine; D009569:Nitric Oxide; D007649:Ketamine; D016291:Dizocilpine Maleate; D026423:S-Nitroso-N-Acetylpenicillamine; D006157:Guanosine Monophosphate; C016837:zinc chloride; D001120:Arginine; D007099:Imipramine; D001205:Ascorbic Acid