关键词: Anogenital Basolateral amygdala Electrophysiology Lipopolysaccharide Low dose Social Sustained inflammation Transition

Mesh : Rats Male Animals Basolateral Nuclear Complex Lipopolysaccharides / pharmacology Amygdala Social Behavior Anxiety Inflammation

来  源:   DOI:10.1007/s00213-023-06308-8

Abstract:
BACKGROUND: Conditions with sustained low-grade inflammation have high comorbidity with depression and anxiety and are associated with social withdrawal. The basolateral amygdala (BLA) is critical for affective and social behaviors and is sensitive to inflammatory challenges. Large systemic doses of lipopolysaccharide (LPS) initiate peripheral inflammation, increase BLA neuronal activity, and disrupt social and affective measures in rodents. However, LPS doses commonly used in behavioral studies are high enough to evoke sickness syndrome, which can confound interpretation of amygdala-associated behaviors.
OBJECTIVE: The objectives of this study were to find a LPS dose that triggers mild peripheral inflammation but not observable sickness syndrome in adult male rats, to test the effects of sustained mild inflammation on BLA and social behaviors. To accomplish this, we administered single doses of LPS (0-100 μg/kg, intraperitoneally) and measured open field behavior, or repeated LPS (5 μg/kg, 3 consecutive days), and measured BLA neuronal firing, social interaction, and elevated plus maze behavior.
RESULTS: Repeated low-dose LPS decreased BLA neuron firing rate but increased the total number of active BLA neurons. Repeated low-dose LPS also caused early disengagement during social bouts and less anogenital investigation and an overall pattern of heightened social caution associated with reduced gain of social familiarity over the course of a social session.
CONCLUSIONS: These results provide evidence for parallel shifts in social interaction and amygdala activity caused by prolonged mild inflammation. This effect of inflammation may contribute to social symptoms associated with comorbid depression and chronic inflammatory conditions.
摘要:
背景:患有持续低度炎症的疾病与抑郁和焦虑并存,并与社交退缩有关。基底外侧杏仁核(BLA)对于情感和社会行为至关重要,并且对炎性挑战敏感。大全身剂量的脂多糖(LPS)引发外周炎症,增加BLA神经元活动,扰乱啮齿动物的社会和情感措施。然而,行为研究中常用的LPS剂量足以引起疾病综合征,这可以混淆杏仁核相关行为的解释。
目的:本研究的目的是在成年雄性大鼠中找到能引发轻度外周炎症但未观察到疾病综合征的LPS剂量。测试持续轻度炎症对BLA和社会行为的影响。要做到这一点,我们给予单剂量的LPS(0-100μg/kg,腹膜内)和测量的开放场行为,或重复的LPS(5μg/kg,连续3天),测量BLA神经元放电,社交互动,和高架加上迷宫行为。
结果:反复低剂量LPS降低了BLA神经元的放电率,但增加了活跃的BLA神经元的总数。反复的低剂量LPS还导致社交发作期间的早期脱离接触和较少的肛门生殖器调查,以及在社交过程中与社交熟悉度降低相关的增强社交谨慎的整体模式。
结论:这些结果为长期轻度炎症引起的社交互动和杏仁核活动的平行变化提供了证据。炎症的这种作用可能导致与共病抑郁症和慢性炎症相关的社会症状。
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