Available data support the notion that cannabinoids, whose therapeutic value is limited due to severe adverse reactions, could be beneficial as adjunctive agents in the management of mood disorders. Polytherapy, which is superior to monotherapy in the terms of effectiveness, usually requires lower doses of the individual components. Therefore, the main objective of our study was to determine whether administration of cannabinoid (CB) receptor ligands would enhance the antidepressant activity of atypical antidepressant drugs, i.e. agomelatine and tianeptine. To evaluate the antidepressant-like potential of the tested combinations, the mouse forced swim test (FST) and the tail suspension test (TST) were used. The HPLC method was applied to assess the brain levels of agomelatine and tianeptine. Both behavioural tests demonstrated that per se an ineffective intraperitoneal dose of oleamide (CB₁ receptor agonist, 5 mg/kg) potentiated the anti-immobility activity of tianeptine (15 mg/kg), whereas AM251 (CB₁ receptor inverse agonist/antagonist, 0.25 mg/kg) enhanced the antidepressant effects of tianeptine and agomelatine (20 mg/kg). Intraperitoneal co-administration of per se inactive doses of AM630 (CB₂ receptor inverse agonist/antagonist) and agomelatine or tianeptine significantly reduced the immobility time of animals only in the FST. CB receptor ligands did not affect the brain levels of the tested atypical antidepressants. In summary, the outcomes of the present study showed that activation and inhibition of CB₁ receptors as well as inhibition of CB₂ receptors may increase the antidepressant activity of tianeptine, whereas only inhibition of CB₁ and CB₂ receptors has a potential to augment the antidepressant activity of agomelatine.

现有数据支持这样一种观点，即大麻素的治疗价值因严重的不良反应而受到限制，作为辅助药物治疗情绪障碍可能是有益的。综合疗法在有效性方面优于单一疗法，通常需要较低剂量的单个成分。因此，我们研究的主要目的是确定大麻素 (CB) 受体配体的给药是否会增强非典型抗抑郁药物（即阿戈美拉汀和噻奈普汀）的抗抑郁活性。为了评估测试组合的抗抑郁样潜力，使用了小鼠强迫游泳试验（FST）和悬尾试验（TST）。应用高效液相色谱法评估阿戈美拉汀和噻奈普汀的脑水平。₁受体激动剂，5 mg/kg）增强了 tianeptine（15 mg/kg）的抗不动活性，而 AM251（CB ₁受体反向激动剂/拮抗剂，0.25 mg/kg）增强了 tianeptine 和 agomelatine 的抗抑郁作用（20毫克/公斤）。本身无活性剂量的 AM630（CB ₂受体反向激动剂/拮抗剂）和阿戈美拉汀或噻奈普汀的腹膜内共同给药仅在 FST 中显着减少了动物的不动时间。CB 受体配体不影响测试的非典型抗抑郁药的脑水平。总之，本研究的结果表明，CB ₁受体的激活和抑制以及 CB _2的抑制受体可能会增加噻奈普汀的抗抑郁活性，而只有抑制 CB ₁和 CB ₂受体才有可能增加阿戈美拉汀的抗抑郁活性。