1. The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization: Implications to the animal model of bipolar disorder.
- Author
-
Valvassori SS, Mariot E, Varela RB, Bavaresco DV, Dal-Pont GC, Ferreira CL, Andersen ML, Tye SJ, and Quevedo J
- Subjects
- Animals, Anxiety chemically induced, Behavior, Animal drug effects, Bipolar Disorder chemically induced, Brain drug effects, Brain-Derived Neurotrophic Factor drug effects, Brain-Derived Neurotrophic Factor metabolism, Corpus Striatum drug effects, Corpus Striatum metabolism, Depression chemically induced, Disease Models, Animal, Frontal Lobe drug effects, Frontal Lobe metabolism, Glial Cell Line-Derived Neurotrophic Factor drug effects, Glial Cell Line-Derived Neurotrophic Factor metabolism, Hippocampus drug effects, Hippocampus metabolism, Locomotion drug effects, Male, Nerve Growth Factor drug effects, Nerve Growth Factor metabolism, Nerve Growth Factors drug effects, Neurotrophin 3 drug effects, Neurotrophin 3 metabolism, Rats, Rats, Wistar, Anxiety metabolism, Bipolar Disorder metabolism, Brain metabolism, Depression metabolism, Dextroamphetamine pharmacology, Nerve Growth Factors metabolism
- 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) 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., (Copyright © 2018. Published by Elsevier B.V.)
- Published
- 2019
- Full Text
- View/download PDF