Participation of NMDA receptors in Fluoxetine effects on memory recognition and the MAPK genes expression in mice.

JUAN ROBLEDO; MARIA BELEN PORETTI; GASPARINI GATICA MAURO; MARIELA F PEREZ; ANA CAROLINA MARTINI; VALERIA PAOLA CARLINI

Congreso; LXVIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC) XXV Jornadas Anuales de la Sociedad Argentina de Biología (SAB) LV Reunión Anual de la Asociación Argentina de Farmacología Experimental (AAFE) VIII Reunión Científica Region; 2023

Chronic fluoxetine (FLU) treatment impairs recognition memory, suggesting that this effect could probably be explained by FLU interference in the MAPK/ERK pathway. In order to elucidate the participation of the N-methyl-D aspartate glutamate receptor (NMDA) and the mitogen-activated protein kinases (Ca ++ -MAMPK) pathway in FLU effects on behavioral memory expression, in the present project adult male Albino?s Swiss mice were divided in groups (n=10/group) and treated for 28 days with saline/saline; NMDA/saline (NMDA: 75mg/Kg/day, i.p), saline/FLU (FLU: 10mg/Kg/day, p.o.) or NMDA/FLU. The last day of treatment mice were tested in the object recognition paradigm (TRO), and then sacrificed and their hipocampus were collected, to study gene expression of MAPK1, MAPK2 and MAPK3, by real time PCR. Data were analyzed by a two-way ANOVA, followed by Bonferroni test. FLU treatment decreases the percentage of exploration of the novel object in the TRO (F=12.59, df=36, p≤0.05), while NMDA treatment significantly increases this parametrer (p≤0.05). Animals treated with FLU and NMDA showed a behavior similar to controls. Regarding genes expression, animals treated with FLU showed a significant decrease in the relative expression of MAPK1 (F 6.65, df=36, p=0.005) and MARK2 (F=9.31, df=36 p≤0.05). Conversely, NMDA administration significantly increased the relative expression of MAPK1 and MARK2 (p≤0.05) in comparison to saline/saline, and the animals administered with MDMA and FLU showed genes expression similar to control. No significant effects were detected on the relative gene expression of MARK3 (F=0.35, df=36, p>0.05).Our results show that the NMDA receptor activation during FLU treatment avoidsFLU-induced memory impairment as well as down-regulation in MAPK/ERK pathway.Whether FLU has direct actions on NMDA receptors to induce both effects or theyare mediated by other effectors that converge in the MAPK/ERK pathway remains tobe elucidated.