Effects of mood stabilizers on hippocampus BDNF levels in an animal model of mania.
There is an emerging body of data suggesting that mood disorders are associated with decreased brain-derived neurotrophic factor (BDNF). The present study aims to investigate the effects of the mood stabilizers lithium (Li) and valproate (VPT) in an animal model of bipolar disorder. In the first experiment (acute treatment), rats were administered D-amphetamine (AMPH) or saline for 14 days, and then between day 8 and 14, rats were treated with either Li, VPT or saline. In the second experiment (maintenance treatment), rats were pretreated with Li, VPT or saline, and then between day 8 and 14, rats were administered AMPH or saline. In both experiments, locomotor activity was measured using the open-field test and BDNF levels were measured in rat hippocampus by sandwich-ELISA. Li and VPT reversed AMPH-induced behavioral effects in the open-field test in both experiments. In the first experiment, Li increased BDNF levels in rat hippocampus. In the second experiment, AMPH decreased BDNF levels and Li and VPT increased BDNF levels in rat hippocampus. Our results suggest that the present model fulfills adequate face, construct and predictive validity as an animal model of mania.
Frey
Benício N
BN
Department of Biochemistry, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600/Anexo, Zip code: 90035-003, Porto Alegre, RS, Brazil.
Andreazza
Ana C
AC
Ceresér
Keila M M
KM
Martins
Márcio R
MR
Valvassori
Samira S
SS
Réus
Gislaine Z
GZ
Quevedo
João
J
Kapczinski
Flávio
F
D000339:Affect / Q000187:drug effects; D000661:Amphetamine / Q000037:antagonists & inhibitors / Q000633:toxicity; D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage*; D001714:Bipolar Disorder / Q000139:chemically induced / Q000188:drug therapy*; D019208:Brain-Derived Neurotrophic Factor / Q000032:analysis / Q000378:metabolism*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008094:Lithium / Q000008:administration & dosage*; D008297:Male; D051381:Rats / Q000378:metabolism*; D017208:Rats, Wistar; D014635:Valproic Acid / Q000008:administration & dosage*
D018692:Antimanic Agents; D019208:Brain-Derived Neurotrophic Factor; D014635:Valproic Acid; D008094:Lithium; D000661:Amphetamine