Fluoxetine alters rat's milk properties causing impact on offspring's development.

Fluoxetine is an antidepressant used to treat several conditions including postpartum depression. This disease causes cognitive, emotional, behavioral and physical changes, negatively affecting the mother, child and family life. However, fluoxetine is excreted in breast milk, causing short and long-term effects on children who were exposed to the drug during lactation, so studies that seek to uncover the consequences of these effects are needed. Thus, the aim of this study was to evaluate the effects of fluoxetine on the nutritional characteristics of milk and on growth and neurobehavioral development of the offspring on a rat model. Lactating rats were divided into 4 groups: control group and three experimental groups, which were treated with different doses of fluoxetine (1, 10 and 20 mg/kg) during the lactation. Dams body weight and milk properties were measured, as well as offspring's growth and physical and neurobehavioral development. Results showed that the use of fluoxetine during lactation decreased dam's body weight and alters milk's properties, leading to a decrease in offspring's growth until adulthood. Therefore, the use of fluoxetine during lactation needs to be cautiously evaluated, with the benefits to the mothers and the associated risk to the offspring carefully balance.

Ketamine causes poor maternal care in rats with postpartum depression and leads to few behavioral and neurochemical alterations on male offspring.

Ketamine is an anesthetic drug that also has antidepressant properties, with quick action. Despite the great number of studies showing its effectiveness as a treatment for major depression, there is little information about its effects on postpartum depression, as pharmacological treatments bring risks to the health of both mother and child. Thus, this study aimed to evaluate the effects of prolonged treatment with subanesthetic doses of ketamine in a rat model of postpartum depression. Female dams were induced to postpartum depression by the maternal separation model from lactating day (LD) 2-12. They were divided into four groups: one control and three experimental groups, which were treated with different doses of ketamine (5, 10 or 20 mg/kg) from LD 2-21 i.p. Maternal studies were conducted from LD5 to LD21 and the offspring studies from postnatal day 2 through 90. Ketamine causes poor maternal care, with few neurochemical alterations. However, the highest dose used in this study had an antidepressant effect. Regarding the male offspring, indirect exposure to ketamine through breast milk caused few behavioral changes during infancy, but they were not permanent, as they faded in adulthood. Nevertheless, this exposure was able to cause alterations in their monoaminergic neurotransmission systems that were found in both infancy and adulthood periods.

Postpartum depression in rats causes poor maternal care and neurochemical alterations on dams and long-lasting impairment in sociability on the offspring.

Postpartum depression is a mentally disabling disease with multifactorial etiology that affects women worldwide. It can also influence child development and lead to behavioral and cognitive alterations. Despite the high prevalence, the disease is underdiagnosed and poorly studied. To study the postpartum depression caused by maternal separation model in rats, dams were separated from their litter for 3 h daily starting from lactating day (LD) 2 through LD12. Maternal studies were conducted from LD5 to LD21 and the offspring studies from postnatal day (PND) 2 through PND90. The stress caused by the dam-offspring separation led to poor maternal care and a transient increase in anxiety in the offspring detected during infancy. The female offspring also exhibited a permanent impairment in sociability during adult life. These changes were associated with neurochemical alterations in the prefrontal cortex and hippocampus, and low TSH concentrations in the dams, and in the hypothalamus, hippocampus and striatum of the offspring. These results indicate that the postpartum depression resulted in a depressive phenotype, changes in the brain neurochemistry and in thyroid economy that remained until the end of lactation. Changes observed in the offspring were long-lasting and resemble what is observed in children of depressant mothers.

Preclinical toxicological study of prolonged exposure to ketamine as an antidepressant.

BACKGROUND: Depression is one of the most common mentally debilitating diseases in the world. Ketamine has been recently identified as a potential novel antidepressant. Further animal model evaluations of the use of ketamine as an antidepressant are necessary to determine safety parameters for clinical use. Therefore, the objective of this study was to perform toxicological tests of prolonged treatment using three different doses of ketamine in adult male rats. METHODS: The animals were divided into four groups: three treated with 5, 10 or 20 mg/kg of ketamine and a control group treated with saline solution. Intraperitoneal route of treatment was administered daily for 3 weeks. Body weight, water and food intake were measured once a week, as well as evaluation of the functional observational battery, which includes methodic monitoring of motor activity, motor coordination, behavioral changes, and sensory/motor reflex responses. Upon completion of treatment period, all animals were euthanized by decapitation followed by immediate collection of samples, which included brain structures and blood for neurochemical, hematological and biochemical analyses. RESULTS: Rats treated with the highest tested dosage (20 mg/kg) of ketamine had lower weight gain in the 1st and 2nd weeks of treatment and all experimental groups had measurable alterations in the serotoninergic system. CONCLUSIONS: Our data indicate that the alterations observed are minor and due to a predicted mechanism of action, which implies that ketamine is a promising drug for repurposing as an antidepressant.

Behavioral and neurochemical characterization of the mlh mutant mice lacking otoconia.

Otoconia are crucial for the correct processing of positional information and orientation. Mice lacking otoconia cannot sense the direction of the gravity vector and cannot swim properly. This study aims to characterize the behavior of mergulhador (mlh), otoconia-deficient mutant mice. Additionally, the central catecholamine levels were evaluated to investigate possible correlations between behaviors and central neurotransmitters. A sequence of behavioral tests was used to evaluate the parameters related to the general activity, sensory nervous system, psychomotor system, and autonomous nervous system, in addition to measuring the acquisition of spatial and declarative memory, anxiety-like behavior, motor coordination, and swimming behavior of the mlh mutant mice. As well, the neurotransmitter levels in the cerebellum, striatum, frontal cortex, and hippocampus were measured. Relative to BALB/c mice, the mutant mlh mice showed 1) reduced locomotor and rearing behavior, increased auricular and touch reflexes, decreased motor coordination and increased micturition; 2) decreased responses in the T-maze and aversive wooden beam tests; 3) increased time of immobility in the tail suspension test; 4) no effects in the elevated plus maze or object recognition test; 5) an inability to swim; and 6) reduced turnover of dopaminergic system in the cerebellum, striatum, and frontal cortex. Thus, in our mlh mutant mice, otoconia deficiency reduced the motor, sensory and spatial learning behaviors likely by impairing balance. We did not rule out the role of the dopaminergic system in all behavioral deficits of the mlh mutant mice.