Effects of perinatal fluoxetine exposure on novelty-induced social and non-social investigation behaviors in a seminatural environment.
Ontology highlight
ABSTRACT:
SUBMITTER: Sylte OC
PROVIDER: S-EPMC8629781 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Several epidemiological studies have reported an association between arsenic exposure and increased rates of psychiatric disorders, including depression, in exposed populations. We have previously demonstrated that developmental exposure to low amounts of arsenic induces depression in adulthood along with several morphological and molecular aberrations, particularly associated with the hippocampus and the hypothalamic-pituitary-adrenal (HPA) axis. The extent and potential reversibility of this toxin-induced damage has not been characterized to date. In this study, we assessed the effects of fluoxetine, a selective serotonin reuptake inhibitor antidepressant, on adult animals exposed to arsenic during development. Perinatal arsenic exposure (PAE) induced depressive-like symptoms in a mild learned helplessness task and in the forced swim task after acute exposure to a predator odor (2,4,5-trimethylthiazoline, TMT). Chronic fluoxetine treatment prevented these behaviors in both tasks in arsenic-exposed animals and ameliorated arsenic-induced blunted stress responses, as measured by corticosterone (CORT) levels before and after TMT exposure. Morphologically, chronic fluoxetine treatment reversed deficits in adult hippocampal neurogenesis (AHN) after PAE, specifically differentiation and survival of neural progenitor cells. Protein expression of BDNF, CREB, the glucocorticoid receptor (GR), and HDAC2 was significantly increased in the dentate gyrus of arsenic animals after fluoxetine treatment. This study demonstrates that damage induced by perinatal arsenic exposure is reversible with chronic fluoxetine treatment resulting in restored resiliency to depression via a neurogenic mechanism.
| S-EPMC4180420 | biostudies-literature
Project description:Maternal separation has been shown to disrupt proper brain development and maturation, having profound consequences on the neuroendocrine systems in charge of the stress response, and has been shown to induce behavioral and cognitive abnormalities. At the behavioral level, maternal separation has been shown to increase offensive play-fighting in juvenile individuals and reduce social interest in adulthood. Since most of the studies that have evaluated the consequences of maternal separation on social behavior have focused on behavioral analysis, there is a need for a further understanding of the neuronal mechanisms underlying the changes in social behavior induced by maternal separation. Therefore, the aim of the present research was to assess the long-term effects of maternal separation on social interaction behavior and to assess the activity of several brain regions involved in the processing of social cues and reward upon social novelty exposure, using c-Fos immunohistochemistry as a marker of neuronal activity. Male Wistar rats were subjected to 4 h maternal separation during the neonatal period, 9:00 h-13:00 h from postnatal day 1 to 21, and exposed to social novelty during adulthood. After social novelty exposure, brains were fixed and coronal sections of the medial amygdala, lateral septum (LS), paraventricular nucleus of the hypothalamus, nucleus accumbens, and medial prefrontal cortex were obtained for c-Fos immunohistochemistry. Maternally separated rats spent less time investigating the novel peer, suggesting that maternal separation reduces social approach motivation. Furthermore, maternal separation reduced the number of c-Fos positive cells of the medial amygdala, paraventricular nucleus of the hypothalamus, LS, nucleus accumbens, and medial prefrontal cortex upon social novelty exposure. These findings suggest that maternal separation can reduce the plastic capacity of several brain nuclei, which constitute a physiological basis for the emergence of behavioral disorders presented later in life reported to be linked to early life adversity.
| S-EPMC8599987 | biostudies-literature
Project description:Mildly stressful early life experiences can potentially impact a broad range of social, cognitive, and physiological functions in humans, nonhuman primates, and rodents. Recent rodent studies favor a maternal-mediation hypothesis that considers maternal-care differences induced by neonatal stimulation as the cause of individual differences in offspring development. Using neonatal novelty exposure, a neonatal stimulation paradigm that dissociates maternal individual differences from a direct stimulation effect on the offspring, we investigated the effect of early exposures to novelty on a diverse range of psychological functions using several assessment paradigms. Pups that received brief neonatal novelty exposures away from the home environment showed enhancement in spatial working memory, social competition, and corticosterone response to surprise during adulthood compared with their home-staying siblings. These functional enhancements in novelty-exposed rats occurred despite evidence that maternal care was directed preferentially toward home-staying instead of novelty-exposed pups, indicating that greater maternal care is neither necessary nor sufficient for these early stimulation-induced functional enhancements. We suggest a unifying maternal-modulation hypothesis, which distinguishes itself from the maternal-mediation hypothesis in that (i) neonatal stimulation can have direct effects on pups, cumulatively leading to long-term improvement in adult offspring; and (ii) maternal behavior can attenuate or potentiate these effects, thereby decreasing or increasing this long-term functional improvement.
| S-EPMC1622887 | biostudies-literature
Project description:The personality trait of curiosity has been shown to increase welfare in humans. If this positive welfare effect is also true for non-humans, animals with high levels of curiosity may be able to cope better with stressful situations than their conspecifics. Before discoveries can be made regarding the effect of curiosity on an animal's ability to cope in their environment, a way of measuring curiosity across species in different environments must be created to standardise testing. To determine the suitability of novel objects in testing curiosity, species from different evolutionary backgrounds with sufficient sample sizes were chosen. Barbary sheep (Ammotragus lervia) n = 12, little penguins (Eudyptula minor) n = 10, ringtail lemurs (Lemur catta) n = 8, red tailed black cockatoos (Calyptorhynchus banksia) n = 7, Indian star tortoises (Geochelone elegans) n = 5 and red kangaroos (Macropus rufus) n = 5 were presented with a stationary object, a moving object and a mirror. Having objects with different characteristics increased the likelihood individuals would find at least one motivating. Conspecifics were all assessed simultaneously for time to first orientate towards object (s), latency to make contact (s), frequency of interactions, and total duration of interaction (s). Differences in curiosity were recorded in four of the six species; the Barbary sheep and red tailed black cockatoos did not interact with the novel objects suggesting either a low level of curiosity or that the objects were not motivating for these animals. Variation in curiosity was seen between and within species in terms of which objects they interacted with and how long they spent with the objects. This was determined by the speed in which they interacted, and the duration of interest. By using the measure of curiosity towards novel objects with varying characteristics across a range of zoo species, we can see evidence of evolutionary, husbandry and individual influences on their response. Further work to obtain data on multiple captive populations of a single species using a standardised method could uncover factors that nurture the development of curiosity. In doing so, it would be possible to isolate and modify sub-optimal husbandry practices to improve welfare in the zoo environment.
| S-EPMC5845565 | biostudies-literature
Project description:Here we show that the novel object recognition test can discriminate between high (HRN, neophobic) and low (LRN, neophilic) novelty responders in zebrafish populations. Especially when we observe the latency to the first entry in the novel object zone, zebrafish did not maintain these behavioral phenotypes in sequential tests and only the HRN group returned to their initial responsive behavior when exposed to fluoxetine. Our results have important implications for behavioral data analysis since such behavioral differences can potentially increase individual response variability and interfere with the outcomes obtained from various behavioral tasks. Our data reinforce the validity of personality determination in zebrafish since we show clear differences in behavior in response to fluoxetine.
| S-EPMC6141609 | biostudies-literature
Project description:Physical inactivity is the third leading cause of the burden of disease for Australian Aboriginal adults. The neighborhood environment and social support are known to influence physical activity (PA) participation. This study examined these factors in relation to achieving PA recommendations in Aboriginal and non-Aboriginal Australians. Cross-sectional data from the 2010 Social, Economic, and Environmental Factor (SEEF) Study in New South Wales, Australia were used to estimate adjusted odds ratios (OR) for Aboriginal versus non-Aboriginal participants for PA-related attributes, including achieving PA recommendations. ORs for achieving PA recommendations were estimated in both groups. Overall, 63.1% of Aboriginal (n = 314) and 65.4% of non-Aboriginal (n = 59,175) participants met PA recommendations. Odds of healthy sleep duration were lower, and receiving GP advice to be active was higher, among Aboriginal versus non-Aboriginal participants. Aboriginal respondents had higher odds of reporting that the crime rate made it unsafe to walk and that local public transport was inaccessible. They had higher odds of disagreeing they have local shops, footpaths or free/low cost recreation facilities. PA correlates were similar in both groups. The factors relating to PA were similar in Aboriginal and non-Aboriginal people. Neighborhood and social features were less PA-favorable for Aboriginal participants suggesting multiple possible avenues for increasing PA in this older population group.
| S-EPMC4929210 | biostudies-literature
Project description:Recently, the putative association between selective serotonin reuptake inhibitor (SSRI) exposure during pregnancy and the development of social disorders in children has gained increased attention. However, clinical studies struggle with the confounding effects of maternal depression typically co-occurring with antidepressant treatment. Furthermore, preclinical studies using an animal model of maternal depression to study effects of perinatal SSRI exposure on offspring social behavior are limited. Therefore, the aim of this study was to investigate effects of perinatal fluoxetine exposure on juvenile and adult social behavior in male and female rat offspring, using an animal model of maternal vulnerability. We exposed heterozygous serotonin transporter (SERT) deficient female rats to early life maternal separation stress, and used this as a model for maternal vulnerability. Control and early life stressed heterozygous serotonin transporter knockout (SERT) dams were treated with the SSRI fluoxetine or vehicle throughout gestation and lactation. Subsequently, both male and female wildtype (SERT+/+) and heterozygous (SERT+/-) rat offspring were tested for pup ultrasonic vocalizations (USVs), juvenile social play behavior and adult social interaction. Fluoxetine treatment of the dams resulted in a reduced total USV duration in pups at postnatal day 6, especially in SERT+/+ males. Perinatal fluoxetine exposure lowered social play behavior in male offspring from both control and early life stressed dams. However, in females a fluoxetine-induced reduction in juvenile play behavior was only present in offspring from control dams. Offspring genotype did not affect juvenile play behavior. Despite fluoxetine-induced behavioral effects at juvenile age, fluoxetine reduced male adult social behavior in offspring from control dams only. Effects of fluoxetine on female adult social behavior were virtually absent. Interestingly, early life stress in dams increased adult social exploration in vehicle exposed SERT+/+ female offspring and total social behavior in fluoxetine exposed adult SERT+/- male offspring. Furthermore, SERT+/- males appeared less social during adulthood compared to SERT+/+ males. Overall, the present study shows that chronic blockade of the serotonin transporter by fluoxetine during early development has a considerable impact on pup USVs, juvenile social play behavior in both male and female offspring, and to a lesser extent on male social interaction in adulthood.
| S-EPMC6423179 | biostudies-literature
Project description:Predators exert considerable top-down pressure on ecosystems by directly consuming prey or indirectly influencing their foraging behaviors and habitat use. Prey is, therefore, forced to balance predation risk with resource reward. A growing list of anthropogenic stressors such as rising temperatures and ocean acidification has been shown to influence prey risk behaviors and subsequently alter important ecosystem processes. Yet, limited attention has been paid to the effects of chronic pharmaceutical exposure on risk behavior or as an ecological stressor, despite widespread detection and persistence of these contaminants in aquatic environments. In the laboratory, we simulated estuarine conditions of the shore crab, Hemigrapsus oregonensis, and investigated whether chronic exposure (60 days) to field-detected concentrations (0, 3, and 30 ng/L) of the antidepressant fluoxetine affected diurnal and nocturnal risk behaviors in the presence of a predator, Cancer productus. We found that exposure to fluoxetine influenced both diurnal and nocturnal prey risk behaviors by increasing foraging and locomotor activity in the presence of predators, particularly during the day when these crabs normally stay hidden. Crabs exposed to fluoxetine were also more aggressive, with a higher frequency of agonistic interactions and increased mortality due to conflicts with conspecifics. These results suggest that exposure to field-detected concentrations of fluoxetine may alter the trade-off between resource acquisition and predation risk among crabs in estuaries. This fills an important data gap, highlighting how intra- and interspecific behaviors are altered by exposure to field concentrations of pharmaceuticals; such data more explicitly identify potential ecological impacts of emerging contaminants on aquatic ecosystems and can aid water quality management.
| S-EPMC5677497 | biostudies-literature
Project description:Early life is a sensitive period, in which enhanced neural plasticity allows the developing brain to adapt to its environment. This plasticity can also be a risk factor in which maladaptive development can lead to long-lasting behavioral deficits. Here, we test how early-life exposure to the selective-serotonin-reuptake-inhibitor (SSRI), fluoxetine, affects motivation, and dopaminergic signaling in adulthood. We show for the first time that mice exposed to fluoxetine in the early postnatal period exhibit a reduction in effort-related motivation. These mice also show blunted responses to amphetamine and reduced dopaminergic activation in a sucrose reward task. Interestingly, we find that the reduction in motivation can be rescued in the adult by administering bupropion, a dopamine-norepinephrine reuptake inhibitor used as an antidepressant and a smoke cessation aid but not by fluoxetine. Taken together, our studies highlight the effects of early postnatal exposure of fluoxetine on motivation and demonstrate the involvement of the dopaminergic system in this process.SIGNIFICANCE STATEMENT The developmental period is characterized by enhanced plasticity. During this period, environmental factors have the potential to lead to enduring behavioral changes. Here, we show that exposure to the SSRI fluoxetine during a restricted period in early life leads to a reduction in adult motivation. We further show that this reduction is associated with decreased dopaminergic responsivity. Finally, we show that motivational deficits induced by early-life fluoxetine exposure can be rescued by adult administration of bupropion but not by fluoxetine.
| S-EPMC8018732 | biostudies-literature
Project description:Behavioral neuroendocrinology has benefited tremendously from the use of a wide range of model organisms that are ideally suited for particular questions. However, in recent years the ability to manipulate the genomes of laboratory strains of mice has led to rapid advances in our understanding of the role of specific genes, circuits and neural populations in regulating behavior. While genome manipulation in mice has been a boon for behavioral neuroscience, the intensive focus on the mouse restricts the diversity in behavioral questions that can be investigated using state-of-the-art techniques. The CRISPR/Cas9 system has great potential for efficiently generating mutants in non-traditional animal models and consequently to reinvigorate comparative behavioral neuroendocrinology. Here we describe the efficient generation of oxytocin receptor (Oxtr) mutant prairie voles (Microtus ochrogaster) using the CRISPR/Cas9 system, and describe initial behavioral phenotyping focusing on behaviors relevant to autism. Oxtr mutant male voles show no disruption in pup ultrasonic vocalization, anxiety as measured by the open field test, alloparental behavior, or sociability in the three chamber test. Mutants did however show a modest elevation in repetitive behavior in the marble burying test, and an impairment in preference for social novelty. The ability to efficiently generate targeted mutations in the prairie vole genome will greatly expand the utility of this model organism for discovering the genetic and circuit mechanisms underlying complex social behaviors, and serves as a proof of principle for expanding this approach to other non-traditional model organisms.
| S-EPMC6506400 | biostudies-literature