Efeito anti-compulsivo sexo e dose dependente da S-ketamina como monoterapia ou adjuvante da fluoxetina em camundongos
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Data
2022-08-19
Autores
Ayub, Júlia Grigorini Mori
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Universidade Federal do Espírito Santo
Resumo
Pharmacological and non-pharmacological therapies for obsessive-compulsive disorder (OCD) are not completely effective for most patients, and when they are, takes time for the improvement to appear. Since a great body of studies supports the involvement of glutamatergic neurotransmission in the neurobiology of OCD, Ketamine, an NMDA glutamatergic receptor antagonist with rapid and sustained antidepressant effect, raises as a potential new anti-OCD drug. Evidence from pre-clinical studies indicates that female mice are more sensitive than male mice to ketamine effects. Additionally, data from our laboratory showed that S-ketamine, an enantiomer of ketamine, induces an anti-compulsive-like effect when administered as monotherapy in male mice. In the present study, we investigated this effect in female mice and the effect of S-ketamine as an adjuvant to fluoxetine, a selective serotonin reuptake inhibitor (SSRI) that is a conventional pharmacological treatment. For this purpose, we used adult female Swiss mice to assess the S-ketamine anti-compulsive-like effect in the marble burring (MBT) and nest building (NBT) tests. S-ketamine 30 mg/kg reduced the compulsive-like behavior of female mice in both animal tests in a bigger dose than the one effective in the previous study for male Swiss mice (10 mg/kg). Adult male and female Swiss mice were used to determine the S-ketamine augmentation effect in a fluoxetine sub-effective dose. The association was effective in reducing the marble-burying behavior of both sexes. Finally, the variation of female sex hormones (estrogen and progesterone) was inferred by estrous cycle and ovariectomy, and no difference was observed in response to S-ketamine in high or low concentrations of these hormones. In conclusion, for both types of treatments, monotherapy and adjuvant treatment, we found that female mice are less sensitive to S-ketamine’s anti-compulsive-like effect than male mice, but the oscillations in female sex hormones concentration do not seem to influence this response.
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S-ketamina , Fêmeas , Camundongos , Ciclo estral , Ovariectomia , Transtorno obsessivo compulsivo , Teste de enterrar esferas