Evidence for the involvement of L-arginine-nitric oxide-cyclic guanosine monophosphate pathway in the antidepressant-like effect of memantine in mice.
This study investigated the involvement of the L-arginine-nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) pathway in the antidepressant-like effect of an acute administration of memantine in the forced swimming test (FST) in mice, since this signaling pathway is supposed to play a significant role in depression. The antidepressant-like effect of memantine (3 mg/kg, i.p.) was prevented by pretreatment with L-arginine (750 mg/kg, i.p.) or S-nitroso-N-acetyl-penicillamine (SNAP, 25 microg/site, i.c.v.), but not with d-arginine (750 mg/kg, i.p.).The treatment of mice with NG-nitro-L-arginine (L-NNA, 0.03 and 0.3 mg/kg, i.p.) potentiated the effect of a subeffective dose of memantine (0.3 mg/kg, i.p.) in the FST. Moreover, the pretreatment of mice with (1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one) (ODQ, 30 pmol/site, i.c.v.) produced a synergistic antidepressant-like effect with subeffective doses of memantine (0.3 and 1 mg/kg, i.p.) in the FST. Furthermore, the reduction in the immobility time elicited by memantine (3 mg/kg, i.p.) in the FST was prevented by pretreatment with sildenafil (5 mg/kg, i.p.). Taken together, the results demonstrate that memantine produced an antidepressant-like effect in the FST that seems to be mediated through an interaction with the L-arginine-NO-cGMP pathway.
Almeida
Rúbia C
RC
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianopolis, 88040-900 SC, Brazil.
Felisbino
Cristiane S
CS
López
Manuela G
MG
Rodrigues
Ana Lúcia S
AL
Gabilan
Nelson H
NH
D000704:Analysis of Variance; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001120:Arginine / Q000502:physiology*; D006152:Cyclic GMP / Q000037:antagonists & inhibitors / Q000502:physiology*; D003863:Depression / Q000188:drug therapy*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D046353:Immobility Response, Tonic / Q000187:drug effects; D008297:Male; D008559:Memantine / Q000008:administration & dosage*; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011687:Purines; D000068677:Sildenafil Citrate; D013450:Sulfones; D013550:Swimming
D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D010879:Piperazines; D011687:Purines; C110881:S-nitro-N-acetylpenicillamine; D013450:Sulfones; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D000068677:Sildenafil Citrate; D010396:Penicillamine; D006152:Cyclic GMP; D008559:Memantine