The role of the NMDA receptors and l-arginine–nitric oxide–cyclic guanosine monophosphate pathway in the antidepressant-like effect of duloxetine in the forced swimming test
| Autor: | Nelson H. Gabilan, Mauricio P. Cunha, Daiane Fátima Engel, Ana Lúcia S. Rodrigues, Andréa D.E. Zomkowski |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
medicine.medical_specialty
Clinical Biochemistry Thiophenes Pharmacology Arginine Duloxetine Hydrochloride Toxicology Receptors N-Methyl-D-Aspartate Biochemistry Mice Behavioral Neuroscience chemistry.chemical_compound Internal medicine medicine Animals Duloxetine Cyclic GMP Forced swimming test Cyclic guanosine monophosphate Swimming Biological Psychiatry Depression Nitric oxide Tail suspension test Antidepressive Agents Endocrinology NMDA Mechanism of action chemistry Antidepressant NMDA receptor Female Serotonin medicine.symptom human activities Behavioural despair test |
| Zdroj: | Pharmacology Biochemistry and Behavior. 103:408-417 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/j.pbb.2012.09.011 |
| Popis: | Duloxetine is a selective serotonin and noradrenaline reuptake inhibitor used as antidepressant. However, its mechanisms of action are not fully understood. This study investigated the effect of duloxetine in the mouse forced swimming test (FST) and in the tail suspension test (TST) and the involvement of the NMDA receptors and the l-arginine–NO–cGMP pathway in its effect in the FST. Duloxetine reduced the immobility time both in the FST and in the TST (dose range of 1–30mg/kg, i.p.), without changing locomotion in an open-field. Duloxetine administered orally (1–30mg/kg) also reduced the immobility time in the FST. The effect of duloxetine (10mg/kg, p.o.) in the FST was prevented by pre-treatment with NMDA (0.1pmol/site, i.c.v.), d-serine (30μg/site, i.c.v.), (l-arginine (750mg/kg, i.p.), S-nitroso-N-acetyl-penicillamine (SNAP, 25μg/site, i.c.v) or sildenafil (5mg/kg, i.p.). The administration of MK-801 (0.001mg/kg, i.p.), 7-nitroindazole (50mg/kg, i.p.), methylene blue (20mg/kg, i.p.) or 1H-[1,2,4]oxadiazole[4,3-a]quinoxalin-1-one (ODQ) (30pmol/site i.c.v.) in combination with a sub-effective dose of duloxetine (0.3mg/kg, p.o.) reduced the immobility time in the FST. Moreover, the administration of duloxetine (10mg/kg) produced a reduction in NOx levels in the hippocampus and cerebral cortex. Altogether the results suggest that the effect of duloxetine in the FST is dependent on either a blockade of NMDA receptors or an inhibition of NO. In addition, our results further reinforce the role of NMDA receptors and l-arginine–NO–cGMP pathway, besides the monoaminergic systems, in the mechanism of action of current prescribed antidepressant agents. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect