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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.
AuthorsGabriel R Fries, Samira S Valvassori, Hugo Bock, Laura Stertz, Pedro Vieira da Silva Magalhães, Edimilson Mariot, Roger B Varela, Marcia Kauer-Sant'Anna, João Quevedo, Flávio Kapczinski, Maria Luiza Saraiva-Pereira
JournalJournal of psychiatric research (J Psychiatr Res) Vol. 68 Pg. 329-36 (Sep 2015) ISSN: 1879-1379 [Electronic] England
PMID26026487 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2015 Elsevier Ltd. All rights reserved.
Chemical References
  • Brain-Derived Neurotrophic Factor
  • Central Nervous System Stimulants
  • RNA, Messenger
  • Amphetamine
Topics
  • Amphetamine (administration & dosage, pharmacology)
  • Amygdala (metabolism)
  • Animals
  • Avoidance Learning
  • Behavior, Animal
  • Bipolar Disorder (chemically induced, metabolism, physiopathology)
  • Brain-Derived Neurotrophic Factor (metabolism)
  • Central Nervous System Stimulants (administration & dosage, pharmacology)
  • Cognition Disorders (metabolism, physiopathology)
  • Disease Models, Animal
  • Habituation, Psychophysiologic
  • Hippocampus (metabolism)
  • Male
  • Memory (drug effects, physiology)
  • Prefrontal Cortex (metabolism)
  • RNA, Messenger
  • Rats
  • Rats, Wistar

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