Considering all mental and addictive disorders, depression is the most responsible for years of life lost due to premature mortality and disability. Antidepressant drugs have limited effectiveness. Depression can be triggered by immune/inflammatory factors. Zinc and paracetamol interfere with immune system and have demonstrated beneficial effects on depression treatment when administered concomitant with antidepressant drugs. The objective of this study was to test zinc and/or paracetamol as treatments of depressive-like behavior, sickness behavior, and anxiety in rats, as well as to understand the central and peripheral mechanisms involved. Sickness behavior and depressive-like behavior were induced in rats with repetitive lipopolysaccharide (LPS, 1 mg/kg for two consecutive days) administrations. Rats received zinc and/or paracetamol for three consecutive days. Sickness behavior (daily body weight and open field general activity); anxiety (light-dark test); depressive-like/antidepressant behavior (forced swim test); plasma corticosterone and interferon (IFN)-gamma levels; and glial fibrillary acidic protein (GFAP) and tyrosine hydroxylase (TH) brain expression were evaluated. LPS induced sickness behavior and depressive-like behavior, as well as elevated IFN-gamma levels and increased GFAP expression. Zinc prevented both behavioral and biochemical impairments. Paracetamol and zinc+paracetamol association induced only slight beneficial effects. Anxiety, corticosterone, and TH do not seem be related with depression and the other behavioral and neuroimmune changes. In conclusion, zinc treatment was beneficial for sickness behavior and depressive-like behavior without concomitant administration of antidepressants. IFN-gamma and GFAP were linked with the expression of sickness behavior and depressive-like behavior and were also involved with the antidepressant effects. Therefore, zinc, IFN-gamma, and GFAP pathways should be considered for depression treatment.

中文翻译：

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锌，但不是扑热息痛，可预防抑郁样行为和疾病行为，并抑制大鼠的干扰素-γ 和星形胶质细胞增生

考虑到所有精神障碍和成瘾性障碍，抑郁症是因过早死亡和残疾而损失数年生命的最主要原因。抗抑郁药的效果有限。抑郁症可由免疫/炎症因素引发。锌和扑热息痛会干扰免疫系统，并且当与抗抑郁药物同时使用时，已证明对抑郁症治疗有益。本研究的目的是测试锌和/或扑热息痛对大鼠抑郁样行为、疾病行为和焦虑的治疗作用，并了解所涉及的中枢和外周机制。重复给予脂多糖（LPS，1mg/kg，连续两天）的大鼠会出现疾病行为和抑郁样行为。大鼠连续三天接受锌和/或扑热息痛。疾病行为（每日体重和野外一般活动）；焦虑（明暗测试）；抑郁样/抗抑郁行为（强迫游泳测试）；血浆皮质酮和干扰素 (IFN)-γ 水平；并评估了胶质纤维酸性蛋白 (GFAP) 和酪氨酸羟化酶 (TH) 脑表达。LPS 诱导疾病行为和抑郁样行为，以及 IFN-γ 水平升高和 GFAP 表达增加。锌防止行为和生化损伤。扑热息痛和锌+扑热息痛联合仅产生轻微的有益作用。焦虑、皮质酮和 TH 似乎与抑郁和其他行为和神经免疫变化无关。综上所述，锌治疗有益于疾病行为和抑郁样行为，而无需同时服用抗抑郁药。IFN-γ 和 GFAP 与疾病行为和抑郁样行为的表达有关，也与抗抑郁作用有关。因此，应考虑锌、IFN-γ 和 GFAP 通路用于抑郁症治疗。