Programa de Pós-Graduação em Bioquímica e Bioprospecção (PPGBBio), Laboratório de Bioquímica e Neurofarmacologia Molecular (LABIONEM), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de Alimentos (CCQFA), Universidade Federal de Pelotas (UFPel), Pelotas, RS, CEP 96010-900, Brasil.
Programa de Pós-Graduação em Química (PPGQ), Laboratório de Síntese de Derivados de Selênio E Telúrio (LabSelen), Departamento de Química, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, CEP 88040-900, Brasil.
Psychopharmacology (Berl). 2021 Oct;238(10):3013-3024. doi: 10.1007/s00213-021-05921-9. Epub 2021 Jul 27.
Depression is a psychiatric disorder that constitutes one of the leading causes of disability worldwide. 2-Phenyl-3-(phenylselanyl)benzofuran (SeBZF1) has been studied as a potential antidepressant drug, but its pharmacological action needs more investigation.
Our aim was to extend information about the antidepressant-like action of SeBZF1 using the mouse tail suspension test (TST). Initial experiments investigated the mechanisms involved in the acute antidepressant-like action of SeBZF1 in male Swiss mice. For this purpose, males received noradrenergic or dopaminergic receptor antagonists before acute SeBZF1 administration (50 mg/kg, per oral). In parallel, effects of combined treatment with SeBZF1 and bupropion at sub-effective doses (1 and 3 mg/kg, respectively) were tested. The next experiments were designed to determine the acute effects of SeBZF1 in females through a dose-response curve (5-50 mg/kg). Lastly, the efficacy of a 7-day repeated treatment with SeBZF1 (1 and 5 mg/kg) in mice of both sexes and its safety were evaluated. TST and the open-field test (OFT) were employed in all behavioral experiments.
Pre-administration of dopaminergic antagonists (SCH23390, a selective DR antagonist; sulpiride, a selective D/DR antagonist; and haloperidol, a non-selective antagonist), but not of adrenergic α, α, and β-R antagonists, blocked the acute antidepressant-like effects of SeBZF1 in males. Co-administration of sub-effective doses of SeBZF1 and bupropion reduced the depressive phenotype. In addition, acute treatment with SeBZF1 at 50 mg/kg produced a reduction of female immobility. Finally, repeated treatment with SeBZF1 (1 and 5 mg/kg) was effective in causing antidepressant-like effects in both sexes. Locomotor activity, plasma transaminases, and urea levels remained unaltered after SeBZF1 exposure.
Our findings provide evidence of the involvement of the dopaminergic system in the acutely antidepressant-like action of SeBZF1 in male mice and reveal the compound efficacy when acute or repeatedly administered in both sexes.
抑郁症是一种精神障碍，构成了全球导致残疾的主要原因之一。2-苯基-3-(苯硒基)苯并呋喃（SeBZF1）已被研究作为一种潜在的抗抑郁药物，但它的药理作用需要更多的研究。
我们的目的是通过小鼠悬尾试验（TST）扩展关于 SeBZF1 的抗抑郁样作用的信息。最初的实验研究了 SeBZF1 在雄性瑞士小鼠中的急性抗抑郁样作用的机制。为此，雄性小鼠在急性 SeBZF1 给药前接受去甲肾上腺素能或多巴胺能受体拮抗剂（分别为 50mg/kg，口服）。同时，还测试了 SeBZF1 与低有效剂量的安非他酮（分别为 1 和 3mg/kg）联合治疗的效果。下一组实验旨在通过剂量反应曲线（5-50mg/kg）确定 SeBZF1 在雌性中的急性作用。最后，评估了 SeBZF1（1 和 5mg/kg）在雌雄小鼠中重复 7 天治疗的疗效及其安全性。所有行为实验均采用悬尾试验（TST）和旷场试验（OFT）。
多巴胺能拮抗剂（SCH23390，一种选择性 DR 拮抗剂；sulpiride，一种选择性 D/DR 拮抗剂；和 haloperidol，一种非选择性拮抗剂）的预给药，但不是肾上腺素能α、α和β-R 拮抗剂，阻断了 SeBZF1 在雄性中的急性抗抑郁样作用。亚有效剂量的 SeBZF1 和安非他酮联合给药可减轻抑郁表型。此外，急性给予 SeBZF1 50mg/kg 可减少雌性的不动性。最后，重复给予 SeBZF1（1 和 5mg/kg）在雌雄两性中均有效引起抗抑郁样作用。暴露于 SeBZF1 后，运动活性、血浆转氨酶和尿素水平保持不变。
我们的研究结果提供了证据，表明多巴胺能系统参与了 SeBZF1 在雄性小鼠中的急性抗抑郁样作用，并揭示了该化合物在两性中的急性或重复给药时的疗效。
