Boosting decision-making in rat models of early-life adversity with environmental enrichment and intranasal oxytocin.

Impaired decision-making constitutes a fundamental issue in numerous psychiatric disorders. Extensive research has established that early life adversity (ELA) increases vulnerability to psychiatric disorders later in life. ELA in human neonates is associated with changes in cognitive, emotional, as well as reward-related processing. Maternal separation (MS) is an established animal model of ELA and has been shown to be associated with decision-making deficits. On the other hand, enriched environment (EE) and intranasal oxytocin (OT) administration have been demonstrated to have beneficial effects on decision-making in humans or animals. Given these considerations, our investigation sought to explore the impact of brief exposure to EE and intranasal OT administration on the decision-making abilities of adolescent rats that had experienced MS during infancy. The experimental protocol involved subjecting rat pups to the MS regimen for 180 min per day from postnatal day (PND) 1 to PND 21. Then, from PND 22 to PND 34, the rats were exposed to EE and/or received intranasal OT (2 µg/µl) for seven days. The assessment of decision-making abilities, using a rat gambling task (RGT), commenced during adolescence. Our findings revealed that MS led to impaired decision-making and a decreased percentage of advantageous choices. However, exposure to brief EE or intranasal OT administration mitigated the deficits induced by MS and improved the decision-making skills of maternally-separated rats. Furthermore, combination of these treatments did not yield additional benefits. These results suggest that EE and OT may hold promise as therapeutic interventions to enhance certain aspects of cognitive performance.

Transmission of behavioral and cognitive impairments across generations in rats subjected to prenatal valproic acid exposure.

BACKGROUND: Autism spectrum disorder (ASD) represents an inheritable neurodevelopmental condition characterized by social communication deficits and repetitive behaviors. Numerous studies have underscored the significant roles played by genetic and environmental factors in the etiology of ASD, and these factors are known to perpetuate behavioral impairments across generations. OBJECTIVES: The primary objective of this study was to assess the behavioral and cognitive attributes in the second filial (F2) generation of male and female rats, with a particular focus on those whose parents had been exposed to valproic acid (VPA) during embryonic development. METHODS: In this study, a cohort of 32 male and 32 female rats from the second filial (F2) generation, referred to as Mother.ASD, Father.ASD, or Both.ASD, was examined. These designations indicate whether the mother, father, or both parents had experienced embryonic exposure to valproic acid (600 mg/kg, i.p.). During adolescence, the F2 pups underwent behavioral and cognitive assessments, including open field testing, marble burying, social interaction evaluations, and Morris water maze tasks. RESULTS: Our data revealed that while both the Mother.ASD and Father.ASD groups, regardless of sex, exhibited elevated anxiety-like behavior in the open field test. Only the Mother.ASD group displayed repetitive behaviors and deficits in social memory. Additionally, spatial memory impairments were observed in both sexes. These findings highlight the transmission of autistic-like behaviors in the offspring of Mother.ASD rats from both sexes. Nevertheless, future research endeavors should be more targeted in identifying the specific genes responsible for this transmission. CONCLUSION: In summary, our findings underscore the transmission of autistic-like behaviors, including anxiety-like behavior, repetitive actions, impairments in social interactions, and deficits in memory, to the offspring of the Mother.ASD group, irrespective of their sex.

The effect of silver nanoparticles on learning and memory in rodents: "a systematic review".

BACKGROUND: Silver nanoparticles (AgNPs) are widely used in medicine owing to their antiseptic activity and inducing cell death. Despite AgNPs' importance in nano-engineering and medical benefits, animal studies have shown silver toxicity can damage multiple organs such as the lungs, liver, kidneys, intestines, and brain. Several investigations revealed the correlation between Ag administration by different methods with impaired cognitive and behavioral abilities. Therefore, this systematic review aimed to conclude on the existing evidence of impairments in learning and memory that were changed in rodents exposed to AgNPs. METHODS: Main searches were retrieved in Google Scholar, Scopus, Web of Science, and PubMed databases from 1979 to 2022. Eligibility Criteria were applied to select and extract 15 articles among 892. RESULTS: Learning and memory abilities of rats and mice in screened studies were evaluated with MWM, NORT, PAL, T-maze, Y-maze, contextual fear conditioning, Radial Arm Maze and Carousel Maze test. Data have shown various sizes from 10 to 100 nm could affect the results of tests among animals exposed to AgNPs compared with control animals. However, in some treatments, results achieved from tests have not demonstrated significant differences between control and treated groups. CONCLUSION: Studies have revealed that treatment with Ag-NPs of different sizes can impair learning and memory skills in rats and mice.

Environmental enrichment and intranasal oxytocin administration reverse maternal separation-induced impairments of prosocial choice behavior.

Adverse early life experiences influence behavioral and physiological functions and increase vulnerability to neuropsychiatric disorders. Maternal separation (MS) is an established animal model that reproduces the features of chronic stress or adverse experiences during early life. Previous studies have been shown that MS may lead to impairments of social behaviors. Here, we investigated the effects of MS on mutual reward preferences in a double T-maze prosocial choice task. Since enriched environment (EE) and intranasal oxytocin (OT) administration have beneficial effects on cognition and social behaviors, in the present study we tested whether these treatments, alone or in combination, would affect prosocial behavior of rats which underwent MS during infancy. Rat pups underwent MS paradigm for 180 min/day from postnatal day (PND) 1-21. From PND 22-34, rats were exposed to an EE and/or received intranasal OT (2 µg/µl, 7 days). Hence, the 8 groups consisted of control (CTRL), MS, CTRL+EE, CTRL+OT and the saline groups. Assessment of prosocial choice behavior was started in adolescence. MS impaired prosocial choice behavior and reduced mutual reward preferences. Getting exposed to EE and intranasal OT administration could overcome MS-induced deficits and promoted mutual reward preferences of MS rats. Combination of short-term EE and OT strengthened prosocial behavior. Obtained results showed that EE and OT may be considered as profitable therapeutic approaches for promoting some aspects of social behavior.

Maternal separation impairs mother's cognition 1 month beyond the separation.

OBJECTIVE: Separation of pups from their dam during the infancy not only has detrimental effects on the pups' brain but also affects dams' behavior. Postpartum stress may affect mothers' cognitive functions. In the present study, by using a 180-min day-1 maternal separation (MS) paradigm, we assessed anxiety-like behavior and locomotor activity of rat dams which experienced separation from postnatal day (PND) 1 until weaning. We tried for the first time to clarify whether such separation impairs dam's performance in the Morris water maze. METHOD: We assessed dams' behavior at three time points: 24 h, 1 week, and 1 month after weaning. Therefore, the six groups consisted of control (CTRL) 24 h, 1 week, and 1 month and MS 24 h, 1 week, and 1 month, which was allocated in this study. RESULTS: Our results revealed that although MS-24 h and MS-1 week groups had intact locomotor activity, MS-1 month group showed less locomotor activity in the open field. Moreover, MS-induced anxiety-like behavior was more pronounced in MS-1 week and MS-1 month dams. Spatial learning and memory was also impaired only in MS-1 month dams. CONCLUSION: We can conclude that MS induces cognitive impairments in dam that may appear not immediately after the separation but a few weeks after such stressful event.

Intergenerational effects of maternal separation on cognitive abilities of adolescent rats.

Early life adversity (ELA) is a predisposing factor for the development of behavioral and emotional disorders later in life. In humans, primates and rodents, interruption in the mother-infant relationships, and disorganized maternal care negatively influence appropriate behavioral responses and may cause cognitive deficits. Epidemiological studies suggest that ELA-induced behavioral alterations can be transmitted across generations. In this study, we investigated the cognitive abilities of male and female rats in the second filial (F2 ) generations whose mother, father, or both of their parents were undergoing a 180 min/day maternal separation (MS) paradigm during infancy (postnatal day (PND) 1-21). Cognitive abilities (in the open field, Morris water maze, and social interaction task) of F2 pups were tested during adolescence. Our results showed that although the mother-MS group of both sexes showed normal cognitive behavior, father-MS female pups showed more anxiety in the open field, and social interaction and spatial memory impaired in this group. These impairments were not pronounced in every detail in father-MS male pups. Moreover, rat pups that both parents experienced MS during infancy, showed normal cognitive behavior. Our data support the idea that MS-induced cognitive impairments could be transmitted across generations. Considerably, the experiences of one's parents could be inherited in the following generation in a sex-dependent manner.