Evidence for the involvement of 5-HT1A receptor in the acute antidepressant-like effect of creatine in mice.
Creatine was previously shown to produce an antidepressant-like effect in the tail suspension test through a modulation of the dopaminergic system. In this study, the mechanisms underlying its antidepressant-like effect were further evaluated by investigating the involvement of the serotonergic system in its effect. The anti-immobility effect of creatine (1mg/kg) was prevented by the pretreatment of mice with p-chlorophenylalanine methyl ester (PCPA; 100mg/kg, i.p., for 4 consecutive days, an inhibitor of serotonin (5-HT) synthesis). Creatine (0.01 mg/kg, sub-effective dose) in combination with sub-effective doses of WAY100635 (0.1mg/kg, s.c., a 5-HT1A receptor antagonist), 8-OH-DPAT (0.1mg/kg, i.p., a 5-HT1A receptor agonist) or selective serotonin reuptake inhibitors fluoxetine (5mg/kg, p.o.), paroxetine (0.1mg/kg, p.o.), citalopram (0.1mg/kg, p.o.) and sertraline (3mg/kg, p.o.) reduced the immobility time in the tail suspension test as compared with either drug alone. These results indicate that the antidepressant-like effect of creatine is likely mediated by an interaction with 5-HT1A receptors. Of note, the present results also indicate that creatine improves the effectiveness of the selective serotonin reuptake inhibitors, a finding that may have therapeutic implications for the treatment of depressive disorders.
Department of Biochemistry, Center of Biological Sciences, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, SC, Brazil.
Mauricio P
MP
Cunha
Francis L
FL
Pazini
Ágatha
Á
Oliveira
Daniele G
DG
Machado
Ana Lúcia S
AL
Rodrigues
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003401:Creatine / Q000494:pharmacology*; D003863:Depression / Q000188:drug therapy*; D003866:Depressive Disorder / Q000188:drug therapy; D019417:Hindlimb Suspension / Q000379:methods; D006801:Humans; D051379:Mice; D017374:Paroxetine / Q000378:metabolism; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism; D058829:Serotonin 5-HT1 Receptor Antagonists / Q000494:pharmacology*
D000928:Antidepressive Agents; D058829:Serotonin 5-HT1 Receptor Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D012701:Serotonin; D017374:Paroxetine; D003401:Creatine