RT Journal Article
T1 Involvement of PI3K, GSK-3β and PPARγ in the antidepressant-like effect of folic acid in the forced swimming test in mice
A1 Budni, Josiane
A1 Lobato, Kelly
A1 Binfaré, Ricardo
A1 Freitas, Andiara
A1 Costa, Ana Paula
A1 Martín De Saavedra Álvarez De Uribarri, María Dolores
A1 Leal, Rodrigo
A1 Lopez, Manuela
A1 Rodrigues, Ana Lucia
AB Preclinical and clinical studies indicate that deficiency in folic acid plays a role in the pathophysiology of depression. Considering that alterations in the signaling pathways that regulate neuroplasticity and cellular survival are implicated in depressive disorders, the present study investigated the involvement of the phosphoinositide 3-kinase (PI3K), glycogen synthase kinase-3 (GSK-3β), and peroxisome proliferator-activated receptor-γ (PPARγ) in the antidepressant-like effect of folic acid in the forced swimming test (FST). The intracerebroventricular (i.c.v.) pre-treatment of mice with LY294002 (10 nmol/site, a PI3K inhibitor) or GW-9662 (1 µg/site, a PPARγ antagonist) prevented the antidepressant-like effect of folic acid (50 mg/kg, p.o.) in the FST. In addition, the administration of subeffective doses of the selective GSK-3β inhibitor, AR-A014418 (3 mg/kg, i.p.), a non-selective GSK-3β inhibitor, lithium chloride (10 mg/kg, p.o) or a PPARγ agonist, rosiglitazone (1 µg/site, i.c.v.) in combination with a subeffective dose of folic acid (10 mg/kg, p.o.) significantly reduced the immobility time in the FST as compared with either drug alone, without altering the locomotor activity. These results indicate that the antidepressant-like effect of folic acid in the FST might be dependent on inhibition of GSK-3β and activation of PPARγ, reinforcing the notion that these are important targets for antidepressant activity.
PB SAGE Publications
SN 0269-8811
YR 2011
FD 2011
LK https://hdl.handle.net/20.500.14352/93440
UL https://hdl.handle.net/20.500.14352/93440
LA eng
NO Budni J, Lobato KR, Binfaré RW, Freitas AE, Costa AP, Martín-de-Saavedra MD, et al. Involvement of PI3K, GSK-3β and PPARγ in the antidepressant-like effect of folic acid in the forced swimming test in mice. J Psychopharmacol 2012;26:714–23. https://doi.org/10.1177/0269881111424456.
DS Docta Complutense
RD 8 abr 2025