Background: Most animals display different defensive behavioral strategies during imminent or potential threats. These responses are relevant for understanding human behavioral disorders. In addition, α1 adrenergic receptors (α1ARs) are blocked by prazosin and regulate a diverse set of behaviors, including alcohol drinking related to anxiety in humans, alcohol intake in rats, responses to strong acute stresses (like restraint), and several forms of cognitive flexibility. However, the role of α1ARs in regulating panic-like escape behavior remains unexplored. Methods: Male and female Wistar rats were chronic alcohol drinkers and age-matched alcohol naïves. Animals received an injection of 0.75 mg/kg of prazosin or vehicle and then were exposed to the elevated T maze (ETM) to evaluate avoidance and escape behavior. One week later, animals underwent the light-dark test (LDT) and open field test. Results: α1AR inhibition with prazosin increased latency for escape in male and female alcohol drinkers, with no significant effects in alcohol-naïve controls. There were also interesting impacts from alcohol drinking, including a decrease in ETM avoidance in female but not male drinkers. In addition, prazosin increased latency to enter the dark in LDT in female drinkers and male naïves. Although prazosin also decreased the number of transitions in males, no differences were found in open-field locomotion. Conclusions: These results suggest that α1ARs mediate escape-like behavior in male and female alcohol drinkers, shedding light on a novel therapy for alcohol problems related to panic and anxiety.

Keywords: alcohol drinking; anxiety; panic; α1 adrenergic receptors.

背景：大多数动物在即将来临或潜在的威胁下会表现出不同的防御行为策略。这些反应对于理解人类行为障碍具有重要意义。此外，α1肾上腺素能受体（α1ARs）被哌唑嗪阻断，并调节一系列行为，包括与焦虑相关的人类酒精摄入、大鼠酒精摄取量、对强烈急性压力（如拘束）的反应以及多种形式的认知灵活性。然而，α1ARs在调节类似恐慌的逃避行为中的作用尚未得到探索。方法：雄性和雌性Wistar大鼠是慢性酒精饮用者，并与年龄匹配的未接触过酒精的大鼠进行比较。动物接受0.75 mg/kg的哌唑嗪或对照液注射，然后暴露于高架T迷宫（ETM）以评估回避和逃避行为。一周后，动物接受了明暗测试（LDT）和开放场测试。结果：用哌唑嗪抑制α1ARs增加了雄性和雌性酒精饮用者的逃避潜伏期，在未接触过酒精的对照组中没有显著影响。饮酒还有其他有趣的影响，包括降低了ETM中雌性但不是雄性的回避行为。此外，哌唑嗪在LDT中延长了雌性饮用者和雄性新手进入黑暗区域的时间。尽管哌唑嗪也减少了男性的转换次数，但在开放场运动中未发现差异。结论：这些结果表明α1ARs调节雄性和雌性酒精饮用者的类似逃避行为，为与恐慌和焦虑相关的酒精问题提供了一种新的治疗方法。

关键词： 酒精摄入；焦虑；恐慌；α1肾上腺素能受体。