The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization: Implications to the animal model of bipolar disorder.
Animals
Anxiety
/ chemically induced
Behavior, Animal
/ drug effects
Bipolar Disorder
/ chemically induced
Brain
/ drug effects
Brain-Derived Neurotrophic Factor
/ drug effects
Corpus Striatum
/ drug effects
Depression
/ chemically induced
Dextroamphetamine
/ pharmacology
Disease Models, Animal
Frontal Lobe
/ drug effects
Glial Cell Line-Derived Neurotrophic Factor
/ drug effects
Hippocampus
/ drug effects
Locomotion
/ drug effects
Male
Nerve Growth Factor
/ drug effects
Nerve Growth Factors
/ drug effects
Neurotrophin 3
/ drug effects
Rats
Rats, Wistar
Amphetamine sensitization
Anxious-like behavior
Bipolar disorder
Depression-like behavior
Manic-like behavior
Neurotrophic factor
Journal
Journal of affective disorders
ISSN: 1573-2517
Titre abrégé: J Affect Disord
Pays: Netherlands
ID NLM: 7906073
Informations de publication
Date de publication:
15 02 2019
15 02 2019
Historique:
received:
04
07
2018
revised:
26
09
2018
accepted:
05
10
2018
entrez:
1
2
2019
pubmed:
1
2
2019
medline:
4
4
2019
Statut:
ppublish
Résumé
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. 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. 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. Although d-AMPH induces manic-like behavior, the mechanisms underlying these effects can also be related to phenotypes of drug abuse. 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.
Sections du résumé
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.
Identifiants
pubmed: 30699853
pii: S0165-0327(18)31450-2
doi: 10.1016/j.jad.2018.10.370
pii:
doi:
Substances chimiques
Brain-Derived Neurotrophic Factor
0
Glial Cell Line-Derived Neurotrophic Factor
0
Nerve Growth Factors
0
Neurotrophin 3
0
Nerve Growth Factor
9061-61-4
Dextroamphetamine
TZ47U051FI
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1106-1113Informations de copyright
Copyright © 2018. Published by Elsevier B.V.