Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, Campus Universitário, Trindade, Florianópolis, SC, 88040-900, Brazil.
Naunyn Schmiedebergs Arch Pharmacol. 2020 Oct;393(10):1931-1939. doi: 10.1007/s00210-020-01910-5. Epub 2020 May 23.
Considering the involvement of GABAergic system in the action of the fast-acting antidepressant ketamine, and that agmatine may exert an antidepressant-like effect through mechanisms similar to ketamine, the purpose of the present study was to evaluate the involvement of GABA and GABA receptors in the antidepressant-like effect of agmatine. The administration of muscimol (0.1 mg/kg, i.p., GABA receptor agonist) or diazepam (0.05 mg/kg, p.o., GABA receptor positive allosteric modulator) at doses that caused no effect in the tail suspension test (TST) combined with a subeffective dose of agmatine (0.0001 mg/kg, p.o.) produced a synergistic antidepressant-like effect in the TST. In another set of experiments, the administration of baclofen (1 mg/kg, i.p., GABA receptor agonist) abolished the reduction of immobility time in the TST elicited by agmatine (0.1 mg/kg, p.o., active dose). In another cohort of animals, treatment with NMDA (0.1 pmol/site, i.c.v.) prevented the antidepressant-like effect of the combined administration of agmatine and muscimol as well as ketamine and muscimol in the TST. Results suggest that the effect of agmatine in the TST may involve an activation of GABA receptors dependent on NMDA receptor inhibition, similar to ketamine, as well as modulation of GABA receptors.
鉴于 GABA 能系统参与了快速抗抑郁药氯胺酮的作用，而胍丁胺可能通过类似于氯胺酮的机制发挥抗抑郁样作用，本研究旨在评估 GABA 和 GABA 受体在胍丁胺抗抑郁样作用中的参与。在尾悬试验（TST）中，给予剂量的 muscimol（0.1mg/kg，腹腔注射，GABA 受体激动剂）或 diazepam（0.05mg/kg，口服，GABA 受体正变构调节剂），这些剂量在 TST 中没有产生作用，与胍丁胺（0.0001mg/kg，口服，亚有效剂量）联合使用产生了协同抗抑郁样作用。在另一组实验中，给予 baclofen（1mg/kg，腹腔注射，GABA 受体激动剂）消除了胍丁胺（0.1mg/kg，口服，有效剂量）引起的 TST 中不动时间的减少。在另一组动物中，用 NMDA（0.1pmol/site，脑室内注射）处理防止了联合给予胍丁胺和 muscimol 以及氯胺酮和 muscimol在 TST 中的抗抑郁样作用。结果表明，胍丁胺在 TST 中的作用可能涉及 NMDA 受体抑制依赖性的 GABA 受体激活，类似于氯胺酮，以及 GABA 受体的调制。
