The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization: Implications to the animal model of bipolar disorder.
J Affect Disord
; 245: 1106-1113, 2019 02 15.
Article
em En
| MEDLINE
| ID: mdl-30699853
ABSTRACT
BACKGROUND:
Bipolar disorder (BD) and substance use disorders share common symptoms, such as behavioral sensitization. Amphetamine-induced behavioral sensitization can serve as an animal model of BD. Neurotrophic factors have an important role in BD pathophysiology. This study evaluated the effects of amphetamine sensitization on behavior and neurotrophic factor levels in the brains of rats.METHODS:
Wistar rats received daily intraperitoneal (i.p) injections of dextroamphetamine (d-AMPH) 2â¯mg/kg or saline for 14 days. After seven days of withdrawal, the animals were challenged with d-AMPH (0.5â¯mg/kg, i.p) and locomotor behavior was assessed. In a second protocol, rats were similarly treated with d-AMPH (2â¯mg/kg, i.p) for 14 days. After withdrawal, without d-AMPH challenge, depressive- and anxiety-like behaviors were evaluated through forced swimming test and elevated plus maze. Levels of brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), neurotrophin 3 (NT-3), neurotrophin 4/5 (NT-4/5) and glial-derived neurotrophic factor (GDNF) were evaluated in the frontal cortex, hippocampus, and striatum.RESULTS:
D-AMPH for 14 days augmented locomotor sensitization to a lower dose of d-AMPH (0.5â¯mg/kg) after the withdrawal. d-AMPH withdrawal induced depressive- and anxious-like behaviors. BDNF, NGF, and GDNF levels were decreased, while NT-3 and NT-4 levels were increased in brains after d-AMPH sensitization.LIMITATIONS:
Although d-AMPH induces manic-like behavior, the mechanisms underlying these effects can also be related to phenotypes of drug abuse.CONCLUSIONS:
Together, vulnerability to mania-like behavior following d-AMPH challenge and extensive neurotrophic alterations, suggest amphetamine-induced behavioral sensitization is a good model of BD pathophysiology.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Ansiedade
/
Transtorno Bipolar
/
Encéfalo
/
Depressão
/
Dextroanfetamina
/
Fatores de Crescimento Neural
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Affect Disord
Ano de publicação:
2019
Tipo de documento:
Article