The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization: Implications to the animal model of bipolar disorder

Samira S. Valvassori, Edemilson Mariot, Roger B. Varela, Daniela V. Bavaresco, Gustavo C. Dal-Pont, Camila L. Ferreira, Monica L. Andersen, Susannah J. Tye, Joao L De Quevedo

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1106-1113
Number of pages8
JournalJournal of Affective Disorders
Volume245
DOIs
StatePublished - Feb 15 2019

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Dextroamphetamine
Nerve Growth Factors
Amphetamine
Bipolar Disorder
Animal Models
Neurotrophin 3
Brain-Derived Neurotrophic Factor
Nerve Growth Factor
Neuroglia
Substance-Related Disorders
Brain
Frontal Lobe
Intraperitoneal Injections
Wistar Rats
Hippocampus
Anxiety
Phenotype

Keywords

  • Amphetamine sensitization
  • Anxious-like behavior
  • Bipolar disorder
  • Depression-like behavior
  • Manic-like behavior
  • Neurotrophic factor

ASJC Scopus subject areas

  • Clinical Psychology
  • Psychiatry and Mental health

Cite this

The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization : Implications to the animal model of bipolar disorder. / Valvassori, Samira S.; Mariot, Edemilson; Varela, Roger B.; Bavaresco, Daniela V.; Dal-Pont, Gustavo C.; Ferreira, Camila L.; Andersen, Monica L.; Tye, Susannah J.; De Quevedo, Joao L.

In: Journal of Affective Disorders, Vol. 245, 15.02.2019, p. 1106-1113.

Research output: Contribution to journalArticle

Valvassori, Samira S. ; Mariot, Edemilson ; Varela, Roger B. ; Bavaresco, Daniela V. ; Dal-Pont, Gustavo C. ; Ferreira, Camila L. ; Andersen, Monica L. ; Tye, Susannah J. ; De Quevedo, Joao L. / The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization : Implications to the animal model of bipolar disorder. In: Journal of Affective Disorders. 2019 ; Vol. 245. pp. 1106-1113.
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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.",
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T2 - Journal of Affective Disorders

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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 - De Quevedo, Joao L

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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.

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