Department of Pharmacology, Ribeirão Preto Medical School, University of São Paulo, São Paulo, Brazil.
School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, UK.
J Psychopharmacol. 2021 Dec;35(12):1523-1535. doi: 10.1177/02698811211058986.
Acute hypoxia, which is panicogenic in humans, also evokes panic-like behavior in male rats. Panic disorder is more common in women and susceptibility increases during the premenstrual phase of the cycle.
We here investigated for the first time the impact of hypoxia on the expression of panic-like escape behavior by female rats and its relationship with the estrous cycle. We also evaluated functional activation of the midbrain panic circuitry in response to this panicogenic stimulus and whether short-term, low-dose fluoxetine treatment inhibits the hyper-responsiveness of females in late diestrus.
Male and female Sprague Dawley rats were exposed to 7% O. Females in late diestrus were also tested after short-term treatment with fluoxetine (1.75 or 10 mg/kg, i.p.). Brains were harvested and processed for c-Fos and tryptophan hydroxylase immunoreactivity in the periaqueductal gray matter (PAG) and dorsal raphe nucleus (DR).
Acute hypoxia evoked escape in both sexes. Overall, females were more responsive than males and this is clearer in late diestrus phase. In both sexes, hypoxia induced functional activation (c-Fos expression) in non-serotonergic cells in the lateral wings of the DR and dorsomedial PAG, which was greater in late diestrus than proestrus (lowest behavioral response to hypoxia). Increased responding in late diestrus (behavioral and cellular levels) was prevented by 1.75, but not 10 mg/kg fluoxetine.
The response of female rats to acute hypoxia models panic behavior in women. Low-dose fluoxetine administered in the premenstrual phase deserves further attention for management of panic disorders in women.
急性缺氧会引起人类恐慌，也会引起雄性大鼠出现类似恐慌的行为。恐慌症在女性中更为常见，而且在月经周期的经前期阶段，易感性会增加。
我们首次研究了缺氧对雌性大鼠出现类似恐慌的逃避行为的影响及其与月经周期的关系。我们还评估了中脑恐慌回路对这种恐慌刺激的功能激活，以及短期、低剂量氟西汀治疗是否抑制了发情后期雌性的过度反应。
雄性和雌性 Sprague Dawley 大鼠暴露于 7% 的 O2 中。发情后期的雌性大鼠也在短期氟西汀（1.75 或 10mg/kg，腹腔注射）治疗后进行测试。采集大脑并处理中脑导水管周围灰质（PAG）和背侧中缝核（DR）中的 c-Fos 和色氨酸羟化酶免疫反应性。
急性缺氧会引起两性的逃避行为。总的来说，雌性比雄性更敏感，在发情后期阶段更为明显。在两性中，缺氧诱导了非血清素能细胞在 DR 的外侧翼和 PAG 的背内侧的功能激活（c-Fos 表达），这种激活在发情后期比发情前期更强（对缺氧的最低行为反应）。1.75mg/kg 的氟西汀可以预防发情后期的反应增加（行为和细胞水平），而 10mg/kg 的氟西汀则不能。
雌性大鼠对急性缺氧的反应模拟了女性的恐慌行为。在经前期阶段给予低剂量氟西汀值得进一步关注，以治疗女性的恐慌症。
