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 AMPHtreated
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