Department of Animal Physiology, Institute of Biology and Biochemistry, Maria Curie Skłodowska University, Akademicka 19, PL 20-033 Lublin, Poland.
Pharmacol Rep. 2011;63(6):1526-32. doi: 10.1016/s1734-1140(11)70716-2.
It is known that tianeptine exhibits antidepressant-like activity. Its influence on the glutamatergic system is also known, but the mechanisms involved in this activity remain to be established. The aim of this study was to investigate the involvement of the glutamate pathway in the antidepressant-like action of tianeptine. We investigated the effects of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor ligands on tianeptine-induced activity in the forced swim test (FST) in mice. The antidepressant-like activity of tianeptine (30 m/kg, ip) was significantly antagonized by D-serine (100 nmol/mouse icv) and NBQX (10 mg/kg, ip). Moreover, low, ineffective doses of the glycine/NMDA site antagonist L-701,324 (1 mg/kg, ip) administered together with low, ineffective doses of tianeptine (20 mg/kg, ip) exhibited a significant reduction of immobility time in the FST. These doses of the examined agents, which did have an effect in the FST, did not alter locomotor activity. The present study indicates that the antidepressant-like activity of tianeptine in the FST involves both NMDA and AMPA receptors and suggests that the interaction between serotonergic and glutamatergic transmission may play an important role in the action of tianeptine.
已知天普汀具有抗抑郁样活性。它对谷氨酸能系统的影响也已被知晓，但该活性涉及的机制仍有待确定。本研究旨在探究谷氨酸途径在天普汀抗抑郁样作用中的参与情况。我们研究了 N-甲基-D-天冬氨酸（NMDA）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）受体配体对天普汀在小鼠强迫游泳试验（FST）中诱导活性的影响。天普汀（30 m/kg，ip）的抗抑郁样活性被 D-丝氨酸（100 nmol/只，icv）和 NBQX（10 mg/kg，ip）显著拮抗。此外，低、无效剂量的甘氨酸/NMDA 位点拮抗剂 L-701,324（1 mg/kg，ip）与低、无效剂量的天普汀（20 mg/kg，ip）联合给药，在 FST 中表现出显著减少不动时间。这些剂量的受试药物在 FST 中具有作用，但不改变运动活性。本研究表明，天普汀在 FST 中的抗抑郁样活性涉及 NMDA 和 AMPA 受体，并表明 5-羟色胺能和谷氨酸能传递之间的相互作用可能在天普汀的作用中发挥重要作用。
