Atorvastatin evokes a serotonergic system-dependent antidepressant-like effect in mice
| Autor: | Mauricio P. Cunha, Tharine Dal-Cim, Gislaine Kuminek, Andréa D.E. Zomkowski, Ana Lúcia S. Rodrigues, Carla I. Tasca, Luisa Bandeira Binder, Fabiana K. Ludka, Leandra C. Constantino |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Serotonin medicine.medical_specialty Ketanserin Atorvastatin Clinical Biochemistry Pharmacology Toxicology Serotonergic Biochemistry Mice Behavioral Neuroscience Internal medicine medicine Animals Pyrroles cardiovascular diseases Biological Psychiatry Sertraline Fluoxetine Depression Chemistry Brain nutritional and metabolic diseases Paroxetine Antidepressive Agents Treatment Outcome Endocrinology Heptanoic Acids Receptors Serotonin lipids (amino acids peptides and proteins) Serotonin Antagonists Reuptake inhibitor medicine.drug |
| Zdroj: | Pharmacology Biochemistry and Behavior. 122:253-260 |
| ISSN: | 0091-3057 |
| DOI: | 10.1016/j.pbb.2014.04.005 |
| Popis: | Atorvastatin is a statin largely used in the treatment of hypercholesterolemia and recently revealed as a neuroprotective agent. The antidepressant-like effect of acute atorvastatin treatment in mice has been previously demonstrated by our laboratory. The purpose of this study was to explore the contribution of the serotonergic system in the antidepressant-like effect of atorvastatin in mice. Data demonstrate that the serotonin (5-HT) depleting agent p-chlorophenylalanine methyl ester (PCPA, 100 mg/kg, i.p.) completely abolished atorvastatin (0.1 mg/kg, p.o.) antidepressant-like effect. Besides atorvastatin, fluoxetine (10 mg/kg, p.o.), a serotonin selective reuptake inhibitor (SSRI) was able to exert an antidepressant-like effect, but any of them changed 5-HT content in the hippocampus or frontal cortex. The 5H-T1A (WAY100635, 0.1 mg/kg, s.c) or the 5-HT2A/2C (ketanserin, 5 mg/kg, s.c.) receptor antagonists prevented atorvastatin antidepressant-like effect. In addition, a combinatory antidepressant-like effect was observed when mice received the co-administration of sub-effective doses of atorvastatin (0.01 mg/kg, p.o.) and the SSRI fluoxetine (5 mg/kg, p.o.), paroxetine (0.1 mg/kg, p.o.) or sertraline (1 mg/kg, p.o.). Taken together, these results indicate that the antidepressant-like effect of atorvastatin depends on the serotonergic system modulation. |
| Databáze: | OpenAIRE |
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