TY - JOUR
T1 - The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization
T2 - Implications to the animal model of bipolar disorder
AU - Valvassori, Samira S.
AU - Mariot, Edemilson
AU - Varela, Roger B.
AU - Bavaresco, Daniela V.
AU - Dal-Pont, Gustavo C.
AU - Ferreira, Camila L.
AU - Andersen, Monica L.
AU - Tye, Susannah J.
AU - Quevedo, João
N1 - Publisher Copyright:
© 2018
PY - 2019/2/15
Y1 - 2019/2/15
N2 - 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) 2 mg/kg or saline for 14 days. After seven days of withdrawal, the animals were challenged with D-AMPH (0.5 mg/kg, i.p) and locomotor behavior was assessed. In a second protocol, rats were similarly treated with D-AMPH (2 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 (0.5 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.
AB - 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) 2 mg/kg or saline for 14 days. After seven days of withdrawal, the animals were challenged with D-AMPH (0.5 mg/kg, i.p) and locomotor behavior was assessed. In a second protocol, rats were similarly treated with D-AMPH (2 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 (0.5 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.
KW - Amphetamine sensitization
KW - Anxious-like behavior
KW - Bipolar disorder
KW - Depression-like behavior
KW - Manic-like behavior
KW - Neurotrophic factor
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U2 - 10.1016/j.jad.2018.10.370
DO - 10.1016/j.jad.2018.10.370
M3 - Article
C2 - 30699853
AN - SCOPUS:85058164210
SN - 0165-0327
VL - 245
SP - 1106
EP - 1113
JO - Journal of Affective Disorders
JF - Journal of Affective Disorders
ER -