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.