Aff ;ective disorders, including anxiety and mood disorders, are a constellation of psychiatric diseases that aff ;ect over 10 % of the world’s population. It has been proposed that drugs that change nicotinic acetylcholine receptor (nAChR) activity can affect mood- and anxiety-related behaviors. Also, neuronal nitric oxide synthase (nNOS) is closely associated with the pathophysiology of these disorders. To limit the potential adverse effects of alteration in cholinergic and nitric oxide (NO) systems, we investigated the combined efficacy of subthreshold doses of nAChR antagonist mecamylamine and NO ligands (L-arginine as agonist and l-NAME as an antagonist) on depression- and anxiety-related behaviors in male NMRI mice. Depression-related behaviors using the forced swim test (FST) and anxiety-like activity using the hole-board test were assessed. In our results, mecamylamine (3 mg/kg) showed antidepressant-like properties, and it also tended to have anxiolytic-like effects, though not significant. Concomitant treatment of subthreshold doses of mecamylamine (1 mg/kg) and l-arginine (25 mg/kg), l-NAME (1 mg/kg), or l-arginine/L-NAME were antidepressive. In contrast, l-arginine/L-NAME alone or in associated with mecamylamine showed anxiogenic-like efficacy. Isobolographic analysis exhibited an additive antidepressant effect of the combined subthreshold doses of mecamylamine and l-arginine, and a synergistic antidepressant effect of the combined subthreshold doses of mecamylamine and l-NAME. It should be noted that mecamylamine (3 mg/kg) elicited hypolocomotion. Our results suggest that mecamylamine produces a better antidepressant efficacy in combination with l-NAME than with l-arginine.

影响性障碍，包括焦虑症和情绪障碍，是一组影响世界 10% 以上人口的精神疾病。有人提出，改变烟碱型乙酰胆碱受体 (nAChR) 活性的药物可以影响情绪和焦虑相关的行为。此外，神经元一氧化氮合酶 (nNOS) 与这些疾病的病理生理学密切相关。为了限制胆碱能和一氧化氮 (NO) 系统改变的潜在不利影响，我们研究了阈下剂量的 nAChR 拮抗剂美加明和 NO 配体（L-精氨酸作为激动剂和l-NAME 作为拮抗剂）对雄性 NMRI 小鼠的抑郁和焦虑相关行为的影响。使用强迫游泳测试 (FST) 评估抑郁相关行为和使用洞板测试评估焦虑样活动。在我们的结果中，美加明 (3 mg/kg) 显示出类似抗抑郁药的特性，并且它也倾向于具有类似抗焦虑药的作用，但并不显着。亚阈值剂量的美加明 (1 mg/kg) 和l-精氨酸 (25 mg/kg)、l -NAME (1 mg/kg) 或l-精氨酸/L-NAME 的伴随治疗具有抗抑郁作用。相比之下，l-精氨酸/L-NAME 单独或与美加明联合显示出类似焦虑的功效。等辐射分析显示出组合的亚阈值剂量美加明和的添加剂抗抑郁作用升精氨酸，并将合并的亚阈值剂量美加明和的协同抗抑郁作用升-NAME。应该指出的是，美加明 (3 mg/kg) 会引起运动减退。我们的结果表明，美加明与l- NAME组合比与l-精氨酸组合产生更好的抗抑郁功效。