Effects of mood stabilizers on hippocampus and amygdala BDNF levels in an animal model of mania induced by ouabain.
There is a body of evidence suggesting that BDNF is involved in bipolar disorder (BD) pathogenesis. Intracerebroventricular (ICV) injection of ouabain (OUA), a specific Na(+)/K(+) ATPase inhibitor, induces hyperlocomotion in rats, and has been used as an animal model of mania. The present study aims to investigate the effects of the lithium (Li) and valproate (VPT) in an animal model of mania induced by ouabain. In the reversal model, animals received a single ICV injection of OUA or cerebrospinal fluid (aCSF). From the day following the ICV injection, the rats were treated for 6 days with intraperitoneal (IP) injections of saline (SAL), Li or VPT twice a day. In the maintenance treatment (prevention model), the rats received IP injections of Li, VPT, or SAL twice a day for 12 days. In the 7th day of treatment the animals received a single ICV injection of either OUA or aCSF. After the ICV injection, the treatment with the mood stabilizers continued for more 6 days. Locomotor activity was measured using the open-field test and BDNF levels were measured in rat hippocampus and amygdala by sandwich-ELISA. Li and VPT reversed OUA-related hyperactive behavior in the open-field test in both experiments. OUA decreased BDNF levels in first and second experiments in hippocampus and amygdala and Li treatment, but not VPT reversed and prevented the impairment in BDNF expression after OUA administration in these cerebral areas. Our results suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.
Jornada
Luciano K
LK
Laboratory of Neurosciences and National Science and Technology Institute for Translational Medicine, Postgraduate Program in Health Sciences, Health Sciences Unit, University of Southern Santa Catarina, 88808-000 Criciúma, SC, Brazil.
Moretti
Morgana
M
Valvassori
Samira S
SS
Ferreira
Camila L
CL
Padilha
Peterson T
PT
Arent
Camila O
CO
Fries
Gabriel R
GR
Kapczinski
Flavio
F
Quevedo
João
J
D000679:Amygdala / Q000187:drug effects* / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D004195:Disease Models, Animal; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D018021:Lithium Chloride / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010042:Ouabain; D051381:Rats; D017208:Rats, Wistar; D014635:Valproic Acid / Q000494:pharmacology / Q000627:therapeutic use
D018692:Antimanic Agents; D019208:Brain-Derived Neurotrophic Factor; D010042:Ouabain; D014635:Valproic Acid; D018021:Lithium Chloride