title: Memory and brain-derived neurotrophic factor after subchronic or chronic amphetamine treatment in an animal model of mania.
abstract: Progression of bipolar disorder (BD) has been associated with cognitive impairment and changes in neuroplasticity, including a decrease in serum brain-derived neurotrophic factor (BDNF). However, no study could examine BDNF levels directly in different brain regions after repeated mood episodes to date. The proposed animal model was designed to mimic several manic episodes and evaluate whether the performance in memory tasks and BDNF levels in hippocampus, prefrontal cortex, and amygdala would change after repeated amphetamine (AMPH) exposure. Adult male Wistar rats were divided into subchronic (AMPH for 7 days) and chronic groups (35 days), mimicking manic episodes at early and late stages of BD, respectively. After open field habituation or inhibitory avoidance test, rats were killed, brain regions were isolated, and BDNF mRNA and protein levels were measured by quantitative real-time PCR and ELISA, respectively. AMPH impaired habituation memory in both subchronic and chronic groups, and the impairment was worse in the chronic group. This was accompanied by increased Bdnf mRNA levels in the prefrontal cortex and amygdala region, as well as reduced BDNF protein in the hippocampus. In the inhibitory avoidance, AMPH significantly decreased the change from training to test when compared to saline. No difference was observed between subchronic and chronic groups, although chronically AMPH-treated rats presented increased Bdnf mRNA levels and decreased protein levels in hippocampus when compared to the subchronic group. Our results suggest that the cognitive impairment related to BD neuroprogression may be associated with BDNF alterations in hippocampus, prefrontal cortex, and amygdala.
authors.affiliation: Bipolar Disorder Program, Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; Laboratory of Genetic Identification and Medical Genetic Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; INCT of Translational Medicine, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: gabrielrfries@gmail.com.
authors.forename: Gabriel R
authors.initials: GR
authors.lastname: Fries
authors.affiliation: INCT of Translational Medicine, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; Laboratory of Neurosciences, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, 88806-000, Criciúma, Santa Catarina, Brazil. Electronic address: samiravalvassori@unesc.net.
authors.forename: Samira S
authors.initials: SS
authors.lastname: Valvassori
authors.affiliation: Laboratory of Genetic Identification and Medical Genetic Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, 90035-903, Rio Grande do Sul, Brazil. Electronic address: hugobock@gmail.com.
authors.forename: Hugo
authors.initials: H
authors.lastname: Bock
authors.affiliation: Bipolar Disorder Program, Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; INCT of Translational Medicine, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA. Electronic address: laurastertz@gmail.com.
authors.forename: Laura
authors.initials: L
authors.lastname: Stertz
authors.affiliation: Bipolar Disorder Program, Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; INCT of Translational Medicine, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; Department of Psychiatry, Universidade Federal Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil. Electronic address: pedromaga2@gmail.com.
authors.forename: Pedro Vieira da Silva
authors.initials: PV
authors.lastname: Magalhães
authors.affiliation: INCT of Translational Medicine, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; Laboratory of Neurosciences, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, 88806-000, Criciúma, Santa Catarina, Brazil. Electronic address: edimilsonmariot@hotmail.com.
authors.forename: Edimilson
authors.initials: E
authors.lastname: Mariot
authors.affiliation: INCT of Translational Medicine, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; Laboratory of Neurosciences, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, 88806-000, Criciúma, Santa Catarina, Brazil. Electronic address: roger.varela@hotmail.com.
authors.forename: Roger B
authors.initials: RB
authors.lastname: Varela
authors.affiliation: Bipolar Disorder Program, Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; INCT of Translational Medicine, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, 90035-903, Rio Grande do Sul, Brazil; Department of Psychiatry, Universidade Federal Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil. Electronic address: mksantanna@gmail.com.
authors.forename: Marcia
authors.initials: M
authors.lastname: Kauer-Sant'Anna
authors.affiliation: INCT of Translational Medicine, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA; Laboratory of Neurosciences, Universidade do Extremo Sul Catarinense, Av. Universitária, 1105, 88806-000, Criciúma, Santa Catarina, Brazil. Electronic address: joq@unesc.net.
authors.forename: João
authors.initials: J
authors.lastname: Quevedo
authors.affiliation: Bipolar Disorder Program, Laboratory of Molecular Psychiatry, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; INCT of Translational Medicine, Hospital de Clinicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; Center for Translational Psychiatry, Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center at Houston, Houston, TX, USA; Department of Psychiatry, Universidade Federal Rio Grande do Sul, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil. Electronic address: flavio.kapczinski@gmail.com.
authors.forename: Flávio
authors.initials: F
authors.lastname: Kapczinski
authors.affiliation: Laboratory of Genetic Identification and Medical Genetic Service, Hospital de Clínicas de Porto Alegre, Rua Ramiro Barcelos, 2350, 90035-903, Rio Grande do Sul, Brazil; Department of Biochemistry, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos, 2600, 90035-903, Rio Grande do Sul, Brazil. Electronic address: mlpereira@hcpa.ufrgs.br.
authors.forename: Maria Luiza
authors.initials: ML
authors.lastname: Saraiva-Pereira
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D000679:Amygdala / Q000378:metabolism*; D000818:Animals; D001362:Avoidance Learning; D001522:Behavior, Animal; D001714:Bipolar Disorder / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003072:Cognition Disorders / Q000378:metabolism* / Q000503:physiopathology; D004195:Disease Models, Animal; D006185:Habituation, Psychophysiologic; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D017397:Prefrontal Cortex / Q000378:metabolism*; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000697:Central Nervous System Stimulants; D012333:RNA, Messenger; D000661:Amphetamine
keywords: Amphetamine; Animal model; BDNF; Bipolar disorder; Mania; Memory