Post-Partum Depression Lactating Rat Model for Evaluating Ketamine’s Safety as a Pharmacotherapeutic Treatment: Roles in Cardiac and Urinary Function

Abstract

Depression is one of the world’s most common and mentally disabling illnesses. Post-partum depression is a subtype of depression that affects one in seven women worldwide. Successful pharmacological treatment must consider the consequences for both, since the mother–child bond is fundamental for the well-being of both mother and infant as well as the general development of the newborn. Changes in maternal physiology and/or behavior can significantly influence the development of breastfed infants. Ketamine has been extensively studied for use as an antidepressant due to its mixed mechanisms of action. Safety and efficacy studies in the cardiovascular and urinary systems of a lactating postpartum depression animal model are essential for contributing toward ketamine’s clinical use in the respective patient population. Thus, this project aimed to study the implications of postpartum maternal exposure to ketamine during lactation on the cardiovascular system of female rats submitted to the depression induction model by maternal separation. This model promotes depressive effects through stress caused by the interruption of mother–infant bond early in the offspring’s life. To achieve depression, each dam was separated from her offspring for 3 h per day, from post-natal day 2 (PND2) to PND12. Experimental groups received daily treatment with either 5, 10, or 20 mg/kg of ketamine intraperitoneally during the lactation period, from PND2 to PND21. Behavioral tests consisted of the maternal and aggressive maternal behavior tests, the olfactory preference test, and the forced swim test. A technique for the detection of catecholamines and indoleamines in the heart muscle was developed for the experimental model groups. The histopathological evaluation was performed on these animals’ cardiac muscles and urinary bladders. Our findings suggest that ketamine is safe for use in postpartum depression and does not induce cardiovascular and/or urinary systems toxicity.

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“…Fukushima et al 25 demonstrated ketamine's safety in cardiovascular and urinary systems through a study involving catecholamine and indoleamine detection in rat cardiac muscles (Table 5).…”

Ketamine role in the treatment of Maternal depression: effects on offspring behaviour

“…). Another study showed that postnatal ketamine exposure prevented depression-like behaviour in maternally separated rat pups (Fukushima et al 2022). While early ndings in offspring are optimistic, rodent timing does not perfectly translate to human neurodevelopment, so further research is essential to ensure ketamine safety.…”