Michal Dubovicky

Effect of Chronic Emotional Stress on Habituation Processes in Open Field in Adult Rats

Abstract: In our previous study, repeated stress in the neonatal period was found to slow habituation in the open field in adult rats. The objective of the present study was to investigate how chronic stress can affect habituation processes in the open field when occurring in adulthood. Animals were exposed to 1 week of immobilization on metal boards followed by 1 week of hypokinesis. After the stress procedure, rats were tested in the open field (once daily in 6‐min sessions for four consecutive days). Immediately after the last open‐field test, animals were decapitated. The rapidity of between‐ and within‐session habituation was lower than in control rats. However, this lowering failed to be statistically significant compared with control rats. On the other hand, time latency to step down from an elevated platform was significantly increased in stress‐exposed animals. Four days after the last stressful event, corticotropin‐releasing hormone mRNA levels in the paraventricular nucleus were significantly increased, indicating a long‐term activation of the hypothalamic‐pituitary‐adrenocortical axis. The results suggest that, in contrast to neonatal stress exposure, chronic emotional stress in adult rats does not represent a risk factor for the alteration of habituation processes.

Perinatal selective serotonin reuptake inhibitor medication (SSRI) effects on social behaviors, neurodevelopment and the epigenome

HIGHLIGHTSSerotonin and SSRIs are mediators of maternal care‐giving behaviors.Perinatal SSRIs affect development of play, social, and reproductive behaviors.Perinatal SSRIs and maternal stress alter the developing serotonergic system.Perinatal SSRIs alter neuroplasticity and epigenetic profiles in offspring. ABSTRACT Recent research has linked early life exposure to selective serotonin reuptake inhibitor medications (SSRIs) to modifications of social behaviors in children. Serotonin is a key regulator of neurodevelopment, social behaviors and mental health, and with the growing use of SSRIs to treat maternal affective disorders during the perinatal period, questions have been raised about the benefits and risks of perinatal SSRI exposure on the developing child. This review will highlight how perinatal SSRIs affect maternal care and neurodevelopmental outcomes related to social affiliative behaviors in offspring; such as play behaviors, social interactions, reproductive behaviors, and maternal care of the next generation. We will also review how early life exposure to SSRIs can alter related neurobiology, and the epigenome. Both clinical research and findings from animal models will be discussed. Understanding the impact of perinatal SSRIs on neurobehavioral outcomes will improve the health and well‐being of subsequent generations.

Subchronic perinatal asphyxia in rats: Embryo–foetal assessment of a new model of oxidative stress during critical period of development

Approximately 3% of annual births suffer from birth asphyxia and one million of these newborns die. The aim of this study was to develop a model for studying subchronic perinatal asphyxia (SPA) in rats. Pregnant animals were exposed to 10.5% O2 during sensitive stages of brain development for 4h a day. Biochemical variables were analysed immediately and 24h after asphyxia. SPA caused significant reduction of foetal weight, produced abnormalities of distal parts of the skeleton, and anomalies in the development of brain ventricles. Time-dependent changes were observed in several parameters indicating adjustment of the developing organism to the delivery. Whereas lactate was elevated immediately after asphyxia, glucose mirrored high energy needs 24h after the insult. Immunohistochemical examination of the placentas revealed overgrowth of acidic glycoconjugates in the extracellular matrix of vascular walls in the animals exposed to asphyxia. We observed the presence of muscle fibres in chorionic plate arteries and also in intraplacental arteries. The present model proved to be useful for the study of asphyxial conditions during pregnancy. As it is non-invasive and allows to control asphyxial conditions, it appears suitable for the screening and investigation of indicators of asphyxia in the mother and foetus.

Animal models of maternal depression for monitoring neurodevelopmental changes occurring in dams and offspring

Abstract Depression is one of the most prevalent and life-threatening forms of mental illness affecting about 20% of the population. Depressive disorder as a biochemical phenomenon, was first recognized in the mid-20th century of research, however the etiology of this disease is still not well understood. Although the need to investigate depressive disorders has emerged from the needs of clinical practice, there are many preclinical studies, which brought new insights into this field of research. During experimental work it was crucial to develop appropriate animal models, where the neurohumoral mechanism was similar to humans. In the past decades, several animal models of maternal depression have been developed. We describe the three most popular rodent models of maternal depression which are based on 1. stress prior to gestation, 2. prenatal stress and 3. early life stress. The above-mentioned animal models appear to fulfill many criteria for a relevant animal model of depression; they alter the regulation of the HPA, induce signs of depression-like behavior and several antidepressant treatments can reverse the state induced by maternal stress. Although, they are not able to model all aspects of maternal depression, they are useful models for monitoring neurodevelopmental changes occurring in dams and offspring.

Risks of using SSRI / SNRI antidepressants during pregnancy and lactation

Abstract At present, affective disorders are among the most commonly diagnosed mental diseases. In pregnancy, they can occur as pre-delivery depression, recurrent depressive disorder or postnatal depression. The estimated prevalence of depressive disorders in pregnancy is approximately 9–16%, with some statistics reporting up to 20%. Approximately 2–3% of pregnant women take antidepressants during pregnancy, and the number of mothers treated increases by birth to 5–7%. Treatment of depression during pregnancy and breastfeeding is a controversial issue, as antidepressants can negatively affect the developing fetus. According to epidemiological studies, the effects of treated depression in pregnancy are related to premature birth, decreased body weight of the child, intrauterine growth retardation, neonatal adaptive syndrome, and persistent pulmonary hypertension. However, untreated depression can adversely affect maternal health and increase the risk of preeclampsia and eclampsia, as well as of subsequent postnatal depression, which can lead to disruption of the mother-child relationship. Based on the above mentioned facts, the basic question arises as to whether or not to treat depression during pregnancy and lactation.

Animal tests for anxiety-like and depression-like behavior in rats

Abstract An animal model of human behavior represents a complex of cognitive and/or emotional processess, which are translated from animals to humans. A behavioral test is developed primarily and specifically to verify and support a theory of cognition or emotion; it can also be used to verify a theory of a psychopathology, but it is not developed for a particular type of psychopathology. The paper reviews tests commonly used in novel drug discovery research. Focus is especially on tests which can evaluate anxiety-like (open-field test, novelty suppressed feeding, elevated plus maze, light/dark box, stressinduced hyperthermia) and depression-like behaviors (forced swim test, tail suspension test, sucrose preference test) as they represent an important methodological tool in pre-clinical as well as in behavioral toxicology studies.