Atorvastatin evokes a serotonergic system-dependent antidepressant-like effect in mice.
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.
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade 88040-900, Florianópolis, SC, Brazil; Curso de Farmácia, Universidade do Contestado, 89460-000 Canoinhas, SC, Brazil.
Fabiana K
FK
Ludka
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade 88040-900, Florianópolis, SC, Brazil.
Leandra Celso
LC
Constantino
Programa de Pós-graduação em Farmácia, Centro de Ciências da Saúde, Universidade Federal de Santa Catarina, Trindade 88040-900, Florianópolis, SC, Brazil.
Gislaine
G
Kuminek
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade 88040-900, Florianópolis, SC, Brazil.
Luisa Bandeira
LB
Binder
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade 88040-900, Florianópolis, SC, Brazil.
Andréa D E
AD
Zomkowski
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade 88040-900, Florianópolis, SC, Brazil.
Maurício P
MP
Cunha
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade 88040-900, Florianópolis, SC, Brazil.
Tharine
T
Dal-Cim
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade 88040-900, Florianópolis, SC, Brazil.
Ana Lúcia S
AL
Rodrigues
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Trindade 88040-900, Florianópolis, SC, Brazil. Electronic address: carla.tasca@ufsc.br.
Carla I
CI
Tasca
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000069059:Atorvastatin; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism*; D006538:Heptanoic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051379:Mice; D011758:Pyrroles / Q000494:pharmacology / Q000627:therapeutic use*; D011985:Receptors, Serotonin / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology; D016896:Treatment Outcome
D000928:Antidepressive Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D012701:Serotonin; D000069059:Atorvastatin
Antidepressant-like effect; Atorvastatin; Serotonergic system; Serotonin; Statin; Tail suspension test