A novel finding on sex-dependent diverse behavioral responses to the anticipation of a threat in a rat model of fear conditioning with the involvement of brain-derived neurotrophic factor (BDNF) in the prefrontal cortex.
📄 Abstract
Evidence has shown significant sex differences in freezing and darting behaviors in a rat model of aversive learning using fear conditioning. The present study explored sex differences in a rat model of aversive learning using a fear-conditioning method via measuring freezing and darting behaviors. Fear conditioning was induced by three footshocks (0.8 mA, 3 s, 30-s interval) paired with an auditory conditioned stimulus (75 dB, 3 s). Extinction was performed by broadcasting 20 auditory conditioned stimuli (75 dB, 3 s, 30-s interval), with no shocks, in three, or four, of five sessions. Freezing and darting behaviors, locomotor activity and time spent in the center squares (anxiety-like behavior) in the open field test, and brain-derived neurotrophic factor (BDNF) in the infralimbic region of the mPFC (medial prefrontal cortex) were evaluated. The results showed both sexes showed a high rate of freezing, with males showing more freezing. Females were more responsive to extinction. Darting behavior was only observed in females and diminished following extinction. Locomotion and anxiety-like behavior were increased and decreased following extinction learning in both sexes, respectively. BDNF expression level in the infralimbic region of the mPFC was increased following extinction learning, with a greater increase in females. In conclusion, we showed that females have a diverse behavioral response to the anticipation of a threat in a rat model of fear conditioning. The important role of BDNF in the modulation of both freezing and darting behaviors was also shown.