Involvement of PKA, MAPK/ERK and CaMKII, but not PKC in the acute antidepressant-like effect of memantine in mice.
This study investigated the cellular signaling pathways involved in the acute antidepressant-like action of memantine in the forced swimming test (FST) in mice. The immobility time in the FST was reduced by memantine (3-10 mg/kg, i.p.). The anti-immobility effect of memantine (3 mg/kg, i.p.) was prevented by pretreatment with H-89 (1 microg/site, i.c.v., an inhibitor of PKA), PD098059 (5 microg/site, i.c.v., an inhibitor of MAPK/ERK), KN-62 (1 microg/site, i.c.v., an inhibitor of CaMKII), but not with chelerythrine (1 microg/site, i.c.v., an inhibitor of PKC). Taken together, these results firstly demonstrate that the acute antidepressant-like effect of memantine seems to be dependent on the cellular signaling modulated by PKA, CaMKII and MAPK/ERK, but not by PKC.
Almeida
Rúbia C
RC
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis 88040-900, SC, Brazil.
Souza
Daniela G
DG
Soletti
Rossana C
RC
López
Manuela G
MG
Rodrigues
Ana Lúcia S
AL
Gabilan
Nelson H
NH
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005260:Female; D008297:Male; D008559:Memantine / Q000494:pharmacology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013315:Stress, Psychological
D000928:Antidepressive Agents; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D008559:Memantine