PMID- 30699853 OWN - NLM STAT- MEDLINE DCOM- 20190403 LR - 20190403 IS - 1573-2517 (Electronic) IS - 0165-0327 (Linking) VI - 245 DP - 2019 Feb 15 TI - The role of neurotrophic factors in manic-, anxious- and depressive-like behaviors induced by amphetamine sensitization: Implications to the animal model of bipolar disorder. PG - 1106-1113 LID - S0165-0327(18)31450-2 [pii] LID - 10.1016/j.jad.2018.10.370 [doi] 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. CI - Copyright (c) 2018. Published by Elsevier B.V. FAU - Valvassori, Samira S AU - Valvassori SS AD - Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil. Electronic address: samiravalvassori@unesc.net. FAU - Mariot, Edemilson AU - Mariot E AD - Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil. FAU - Varela, Roger B AU - Varela RB AD - Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil. Electronic address: roger.varela@hotmail.com. FAU - Bavaresco, Daniela V AU - Bavaresco DV AD - Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil. FAU - Dal-Pont, Gustavo C AU - Dal-Pont GC AD - Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil. FAU - Ferreira, Camila L AU - Ferreira CL AD - Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil. FAU - Andersen, Monica L AU - Andersen ML AD - Departamento de Psicobiologia, Universidade Federal de Sao Paulo, Sao Paulo, SP, Brazil. FAU - Tye, Susannah J AU - Tye SJ AD - Queensland Brain Institute, The University of Queensland, St Lucia, QLD 4072, Australia. FAU - Quevedo, Joao AU - Quevedo J AD - Translational Psychiatry Laboratory, Graduate Program in Health Sciences, University of Southern Santa Catarina (UNESC), Criciuma, SC, Brazil; Center of Excellence on Mood Disorders, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA; Neuroscience Graduate Program, The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences, Houston, TX, USA; Translational Psychiatry Program, Department of Psychiatry and Behavioral Sciences, McGovern Medical School, The University of Texas Health Science Center at Houston (UTHealth), Houston, TX, USA. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20181129 PL - Netherlands TA - J Affect Disord JT - Journal of affective disorders JID - 7906073 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Glial Cell Line-Derived Neurotrophic Factor) RN - 0 (Nerve Growth Factors) RN - 0 (Neurotrophin 3) RN - 9061-61-4 (Nerve Growth Factor) RN - TZ47U051FI (Dextroamphetamine) SB - IM MH - Animals MH - Anxiety/chemically induced/*metabolism MH - Behavior, Animal/drug effects MH - Bipolar Disorder/chemically induced/*metabolism MH - Brain/drug effects/*metabolism MH - Brain-Derived Neurotrophic Factor/drug effects/metabolism MH - Corpus Striatum/drug effects/metabolism MH - Depression/chemically induced/*metabolism MH - Dextroamphetamine/*pharmacology MH - Disease Models, Animal MH - Frontal Lobe/drug effects/metabolism MH - Glial Cell Line-Derived Neurotrophic Factor/drug effects/metabolism MH - Hippocampus/drug effects/metabolism MH - Locomotion/drug effects MH - Male MH - Nerve Growth Factor/drug effects/metabolism MH - Nerve Growth Factors/drug effects/*metabolism MH - Neurotrophin 3/drug effects/metabolism MH - Rats MH - Rats, Wistar OTO - NOTNLM OT - Amphetamine sensitization OT - Anxious-like behavior OT - Bipolar disorder OT - Depression-like behavior OT - Manic-like behavior OT - Neurotrophic factor EDAT- 2019/02/01 06:00 MHDA- 2019/04/04 06:00 CRDT- 2019/02/01 06:00 PHST- 2018/07/04 00:00 [received] PHST- 2018/09/26 00:00 [revised] PHST- 2018/10/05 00:00 [accepted] PHST- 2019/02/01 06:00 [entrez] PHST- 2019/02/01 06:00 [pubmed] PHST- 2019/04/04 06:00 [medline] AID - S0165-0327(18)31450-2 [pii] AID - 10.1016/j.jad.2018.10.370 [doi] PST - ppublish SO - J Affect Disord. 2019 Feb 15;245:1106-1113. doi: 10.1016/j.jad.2018.10.370. Epub 2018 Nov 29.