Department of Physiology, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University.
Department of Pharmacology, School of Medicine, Tehran University of Medical Sciences.
Behav Pharmacol. 2024 Apr 1;35(2-3):55-65. doi: 10.1097/FBP.0000000000000729. Epub 2023 May 26.
We investigated the effects of histamine and GABA A receptor agents on pain and depression-like behaviors and their interaction using a tail-flick test and the forced swimming test (FST) in male mice. Our data revealed that intraperitoneal administration of muscimol (0.12 and 0.25 mg/kg) increased the percentage of maximum possible effect (%MPE) and area under the curve (AUC) of %MPE, indicating an antinociceptive response. Intraperitoneal injection of bicuculline (0.5 and 1 mg/kg) decreased %MPE and AUC of %MPE, suggesting hyperalgesia. Moreover, muscimol by reducing the immobility time of the FST elicited an antidepressant-like response but bicuculline by enhancing the immobility time of the FST caused a depressant-like response. Intracerebroventricular (i.c.v.) microinjection of histamine (5 µg/mouse) enhanced %MPE and AUC of %MPE. i.c.v. infusion of histamine (2.5 and 5 µg/mouse) decreased immobility time in the FST. Co-administration of different doses of histamine along with a sub-threshold dose of muscimol potentiated antinociceptive and antidepressant-like responses produced by histamine. Cotreatment of different doses of histamine plus a noneffective dose of bicuculline reversed antinociception and antidepressant-like effects elicited by histamine. Cotreatment of histamine, muscimol, and bicuculline reversed antinociceptive and antidepressant-like behaviors induced by the drugs. The results demonstrated additive antinociceptive and antidepressant-like effects between histamine and muscimol in mice. In conclusion, our results indicated an interaction between the histaminergic and GABAergic systems in the modulation of pain and depression-like behaviors.
我们使用尾部闪烁测试和强迫游泳测试（FST）在雄性小鼠中研究了组胺和 GABA A 受体激动剂对疼痛和抑郁样行为的影响及其相互作用。我们的数据显示，腹腔内给予 muscimol（0.12 和 0.25mg/kg）增加了最大可能效应（%MPE）的百分比和 %MPE 的曲线下面积（AUC），表明有镇痛反应。腹腔内注射 bicuculline（0.5 和 1mg/kg）降低了 %MPE 和 %MPE 的 AUC，表明存在痛觉过敏。此外，muscimol 通过减少 FST 的不动时间产生抗抑郁样反应，但 bicuculline 通过增加 FST 的不动时间引起抑郁样反应。侧脑室（i.c.v.）微注射组胺（5µg/只）增强了 %MPE 和 %MPE 的 AUC。i.c.v.输注组胺（2.5 和 5µg/只）减少了 FST 中的不动时间。给予不同剂量的组胺与给予亚阈值剂量的 muscimol 共同给药增强了组胺产生的镇痛和抗抑郁样反应。给予不同剂量的组胺加无效剂量的 bicuculline 共同处理逆转了组胺引起的镇痛和抗抑郁样作用。组胺、muscimol 和 bicuculline 的共同处理逆转了药物引起的镇痛和抗抑郁样行为。结果表明，组胺和 muscimol 之间存在镇痛和抗抑郁样作用的相加作用。总之，我们的结果表明组胺能和 GABA 能系统在调节疼痛和抑郁样行为方面存在相互作用。
