Department of Physiology, National Cheng Kung University College of Medicine, Tainan, 701, Taiwan, Republic of China.
Institute of Basic Medical Sciences, National Cheng Kung University College of Medicine, Tainan, 701, Taiwan, Republic of China.
Psychopharmacology (Berl). 2021 Oct;238(10):2851-2865. doi: 10.1007/s00213-021-05901-z. Epub 2021 Jun 28.
This study was undertaken to assess the modulating effects of (1) pre-exposure to repeated social disruption and (2) group testing on writhing associated with visceral pain induced by intraperitoneal administration of acetic acid.
Six consecutive days of social disruption were used to prime for stress, while group testing referred to 3 mouse cage-mates receiving the acetic acid-induced writhing test as a group.
Social disruption-induced stress-pre-exposed mice displayed a greater number acid-induced writhes compared to mice not receiving the pre-exposure. However, mice displayed fewer acid-induced writhes in a triad group vs. individually, suggesting group-mediated writhing-reducing effects. Likewise, group testing prevented the stress pre-exposure escalation in acid-induced writhes. Additional studies revealed that the stress-pre-exposed mice had increased expression in accumbal TRPV1 receptors. Systemic (0.25 mg/kg) and bilateral intra-accumbal (0.2 ng/0.2 µl/side) administration of SB366791, a TRPV1 receptor antagonist, reliably prevented the stress pre-exposure escalation in acid-induced writhing; SB366791 treatment alone did not affect acid-induced writhing, stress pre-exposure anxiety-like behavior, or the group testing effects. Furthermore, lower neuronal activation was found in the medial septal nucleus in group vs. individual tested mice. Intra-medial septum (0.2 µg/0.5 µl) infusion with bicuculline, a GABAA receptor antagonist, effectively prevented group-mediated writhing-reducing effects, but not individual acid-induced writhing effects.
These findings suggest that social disruption-induced stress pre-exposure may upregulate accumbal TRPV1 receptor expression and consequently aggravate acid-induced writhing. Group testing prevents such stress pre-exposure escalation of acid-induced writhing most likely by strengthening the GABAergic inhibition on local neural activity in the medial septum.
本研究旨在评估（1）预先暴露于反复的社交中断和（2）小组测试对腹腔内给予醋酸引起的内脏痛相关扭体的调制作用。
使用连续 6 天的社交中断来引发应激，而小组测试是指 3 只同笼的老鼠作为一组接受醋酸诱导的扭体测试。
与未接受预暴露的老鼠相比，社交中断引起的应激预暴露老鼠表现出更多的酸诱导扭体。然而，与单独测试相比，在小组中老鼠表现出较少的酸诱导扭体，表明小组介导的扭体减少效应。同样，小组测试防止了应激预暴露在酸诱导扭体中的加剧。进一步的研究表明，应激预暴露老鼠的伏隔核 TRPV1 受体表达增加。全身（0.25mg/kg）和双侧伏隔核内（0.2ng/0.2µl/侧）给予 TRPV1 受体拮抗剂 SB366791，可靠地防止了酸诱导扭体中应激预暴露的加剧；SB366791 单独治疗不会影响酸诱导扭体、应激预暴露焦虑样行为或小组测试效应。此外，在小组测试的老鼠的中隔核中发现较低的神经元激活。内侧隔核（0.2µg/0.5µl）内给予 GABA A 受体拮抗剂荷包牡丹碱，可有效防止小组介导的扭体减少效应，但不能防止个体酸诱导扭体效应。
这些发现表明，社交中断引起的应激预暴露可能上调伏隔核 TRPV1 受体表达，从而加剧酸诱导扭体。小组测试通过增强内侧隔核局部神经活动的 GABA 能抑制作用，防止了这种应激预暴露对酸诱导扭体的加剧。
