Physiology & behavior · 2026
Sex-dependent behavioral and prefrontal BDNF mRNA responses to extinction training and short-term citalopram after fear conditioning in rats.
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Taghavi Elnaz, Eslami Maryam, Yekta Batool Ghorbani, Gholami Mahdieh, Vaseghi Salar
Аннотация
BACKGROUND: Fear conditioning is widely used to model selected PTSD-relevant fear-related responses in rodents, particularly persistent freezing after an aversive cue. However, this paradigm does not reproduce the full clinical syndrome of PTSD. The present study compared extinction training, short-term citalopram treatment, and their combination in male and female rats, with behavioral outcomes and prefrontal BDNF mRNA expression evaluated as sex-dependent readouts.
METHODS: Male and female Wistar rats were subjected to auditory fear conditioning using three footshocks (0.8 mA, 3 s each; 30 s inter-shock interval), each preceded by a 75 dB auditory cue. Extinction training and/or citalopram (30 mg/kg, i.p.) were administered at 1 h, 24 h, and 48 h after the onset of fear conditioning. Freezing behavior, open-field locomotor activity and rearing, and hot-plate nociceptive latency were assessed after the intervention period. Prefrontal BDNF mRNA expression was quantified by RT-qPCR in selected groups.
RESULTS: Extinction training reduced freezing behavior in both sexes, and the combined citalopram + extinction group showed an additional reduction compared with extinction alone in males. Citalopram alone did not significantly reduce freezing under the present short-term dosing schedule. Locomotor activity was not significantly changed within either sex. Rearing increased after extinction-based intervention, whereas nociceptive latency decreased after extinction and citalopram + extinction. Prefrontal BDNF mRNA expression was unchanged in males but increased in females after extinction and citalopram + extinction.
CONCLUSIONS: These findings support sex-dependent behavioral and molecular responses to extinction-based intervention after fear conditioning. The molecular findings should be interpreted as exploratory because BDNF was assessed only at the mRNA level, in selected groups, and with a small sample size (n = 3/group).
METHODS: Male and female Wistar rats were subjected to auditory fear conditioning using three footshocks (0.8 mA, 3 s each; 30 s inter-shock interval), each preceded by a 75 dB auditory cue. Extinction training and/or citalopram (30 mg/kg, i.p.) were administered at 1 h, 24 h, and 48 h after the onset of fear conditioning. Freezing behavior, open-field locomotor activity and rearing, and hot-plate nociceptive latency were assessed after the intervention period. Prefrontal BDNF mRNA expression was quantified by RT-qPCR in selected groups.
RESULTS: Extinction training reduced freezing behavior in both sexes, and the combined citalopram + extinction group showed an additional reduction compared with extinction alone in males. Citalopram alone did not significantly reduce freezing under the present short-term dosing schedule. Locomotor activity was not significantly changed within either sex. Rearing increased after extinction-based intervention, whereas nociceptive latency decreased after extinction and citalopram + extinction. Prefrontal BDNF mRNA expression was unchanged in males but increased in females after extinction and citalopram + extinction.
CONCLUSIONS: These findings support sex-dependent behavioral and molecular responses to extinction-based intervention after fear conditioning. The molecular findings should be interpreted as exploratory because BDNF was assessed only at the mRNA level, in selected groups, and with a small sample size (n = 3/group).