Possible antidepressant effects of ketamine in lactating rats: evaluation of implications for the offspring

Author(s)

Gabriel Ramos de Abreu

• Document type: Master's Dissertation
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Faculdade de Medicina Veterinária e Zootecnia (FMVZ/SBD)
• Defense date: 2020-05-08

Examining board members

Helenice de Souza Spinosa; Esther Lopes Ricci Adari Camargo; Natalia Moreira

• Advisor: Helenice de Souza Spinosa; André Rinaldi Fukushima

Abstract

Postpartum depression is defined as an episode of major depression disorder that occurs in the period following birth. This disease affects one in seven women and is the main complication of childbirth; the available treatment consists of a combination of psychotherapies and pharmacological treatment, being necessary to consider the consequences that this treatment may have on the lactating mother and the progeny. The mother-infant bond is fundamental to the overall development of the progeny and, therefore, changes in maternal behavior can generate permanent disturbances in the pups. Studies have shown that maternal depression on the first six months post-partum is associated with behavioral problems in kids from childhood to adolescence. Ketamine has been extensively studied for use as an antidepressant due to its mixed mechanism of action. Taking in consideration that there is a tendency to increase the clinical use of ketamine and that there is little information about the ideal dose and route of administration for its use as an antidepressant, as well as the safety and efficacy of a treatment during the postnatal period, more studies are needed on the use of this drug for this purpose, in order to contribute to its safer clinical use. Thus, the objective of this work was to study the effects of the maternal separation model to induce postpartum depression in puppies in childhood and adulthood, as well as to study the effects of prolonged treatment of mothers with ketamine in puppies in childhood and adulthood. For this, lactating rats were induced to postpartum depression by the model of maternal separation of postnatal day (PND) 2 to 12 and treated with different doses of ketamine (5, 10 and 20 mg / kg) intraperitoneally from PND2 to 21. A behavioral assessment was conducted, as well as neurochemical, biochemical and blood count of puppies in childhood (PND21) and adulthood (PND 60 to 90). The results showed that the maternal separation model caused small changes in the neurochemistry of the hippocampus and the striatum of the puppies in adulthood; the other parameters evaluated did not change. Regarding ketamine, the results showed that the different doses used caused behavioral changes in the open field and in the light / dark box, indicating the anxiogenic effect of this drug. The neurochemical analysis showed an increase in the activity of the dopaminergic system, both in young and adult puppies, suggesting that ketamine has an effect on this neurotransmission system. The biochemical and blood count parameters did not change due to the treatment with ketamine. (AU)

• FAPESP's process: 18/05397-0 - Possible antidepressive effects of ketamine in lactating rats: implications on the PROLE
• Grantee: Gabriel Ramos de Abreu
• Support Opportunities: Scholarships in Brazil - Master