Cognitive asymmetry in rats in response to emergent vs. disappearing affordances.

This study examines the effects of novel environmental changes on the behavior of rats in an experimental chamber. We hypothesized that newly discovered opportunities, detected by the animal's cognitive system, would motivate greater investigation of environmental changes than comparable changes that prevent a given behavior. Three experiments differed in the emergence vs. elimination of affordances represented by open or closed tunnels. In Experiment 1, rats were habituated to a chamber with all four tunnels closed, and then two tunnels were opened. In Experiment 2, rats were habituated to a chamber where all four tunnels were open, and then two tunnels were closed. In Experiment 3, rats were habituated to a chamber with two open tunnels on one side, and two closed tunnels on the other. Then, the arrangement of open and closed tunnels was swapped. Results of the Exp. 1 show that the rats responded by spending more time near the newly opened tunnels and less time near the closed tunnels, the central zone, and the transporter. This suggests that rats are more motivated to investigate the environmental change combined with the emergent affordance (opening of the tunnels) than the environmental change alone. In Exp. 2, the rats responded by spending more time near the open tunnels and less time in the central zone. This suggests that the rats are more triggered by the available affordances (open tunnels) than by the environmental change (closed tunnels). Finally, in Exp. 3, the rats responded by spending more time near the newly opened tunnels and less near the central zone. However, they did not spend less time near the newly closed tunnels. These results suggest that rats process both the novelty itself and the emergence/disappearance of available affordances. The results are discussed regarding the cognitive asymmetry in the perception of emergent vs. disappearing affordances. It is proposed that the rat's cognitive system is specialized for detecting newly emergent environmental opportunities/affordances rather than novelty in general.

2,5-Dimethoxy-4-iodoamphetamine and altanserin induce region-specific shifts in dopamine and serotonin metabolization pathways in the rat brain.

PURPOSE: For understanding the neurochemical mechanism of neuropsychiatric conditions associated with cognitive deficits it is of major relevance to elucidate the influence of serotonin (5-HT) agonists and antagonists on memory function as well dopamine (DA) and 5-HT release and metabolism. In the present study, we assessed the effects of the 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI) and the 5-HT2A receptor altanserin (ALT) on object and place recognition memory and cerebral neurotransmitters and metabolites in the rat. METHODS: Rats underwent a 5-min exploration trial in an open field with two identical objects. After systemic injection of a single dose of either DOI (0.1 mg/kg), ALT (1 mg/kg) or the respectice vehicle (0.9 % NaCl, 50 % DMSO), rats underwent a 5-min test trial with one of the objects replaced by a novel one and the other object transferred to a novel place. Upon the assessment of object exploration and motor/exploratory behaviors, rats were sacrificed. DA, 5-HT and metabolite levels were analyzed in cingulate (CING), caudateputamen (CP), nucleus accumbens (NAC), thalamus (THAL), dorsal (dHIPP) and ventral hippocampus (vHIPP), brainstem and cerebellum with high performance liquid chromatography. RESULTS: DOI decreased rearing but increased head-shoulder motility relative to vehicle. Memory for object and place after both DOI and ALT was not different from vehicle. Network analyses indicated that DOI inhibited DA metabolization in CING, CP, NAC, and THAL, but facilitated it in dHIPP. Likewise, DOI inhibited 5-HT metabolization in CING, NAC, and THAL. ALT facilitated DA metabolization in the CING, NAC, dHIPP, vHIPP, and CER, but inhibited it in the THAL. Additionally, ALT facilitated 5-HT metabolization in NAC and dHIPP. CONCLUSIONS: DOI and ALT differentially altered the quantitative relations between the neurotransmitter/metabolite levels in the individual brain regions, by inducing region-specific shifts in the metabolization pathways. Findings are relevant for understanding the neurochemistry underlying DAergic and/or 5-HTergic dysfunction in neurological and psychiatric conditions.

Associations of Early-Life Deprivation and Threat with Exploratory Behavior: Moderated Mediation Models of Sensation Seeking and Executive Function.

Exploratory behavior, as a crucial aspect of decision-making, plays an indispensable role in maximizing long-term benefits and is, therefore, essential in promoting adolescents' psychological well-being and social adaptation. Recent studies have shown that this adaptive behavior is influenced by previous early experiences. However, little was known about the associations between specific types of childhood maltreatment and exploratory behavior and the roles of individual motivational and cognitive factors in these relationships. The present study aimed to examine whether the subtypes of maltreatment, that is, threat and deprivation, would influence adolescents' exploratory behavior, the mediating role of sensation seeking, and the moderating role of executive function. Using a sample of 720 Chinese adolescents (Mage = 13.29, SDage = 0.82, 54.8% female), we found that sensation seeking fully mediated the relationship between threat and exploratory behavior. That is, adolescents who experienced threat were more likely to increase sensation seeking, which further promote exploratory activities. Moreover, executive function was a second-stage moderator of this full mediation pathway, with the mediating effect of sensation seeking between threat and exploratory behavior increasing with the enhancement of executive function. However, we did not observe the mediating effect of sensation seeking and the second-stage moderating effect of executive function on the relationship between deprivation and exploration. Considering the distinct impact mechanisms of threat and deprivation on exploratory behavior, our study provides empirical support for the Dimensional Model of Adversity and Psychopathology, and highlights the critical role of sensation seeking and the necessity of implementing executive function interventions for those experiencing threat experiences.

The Impact of C-3 Side Chain Modifications on Kynurenic Acid: A Behavioral Analysis of Its Analogs in the Motor Domain.

The central nervous system (CNS) is the final frontier in drug delivery because of the blood-brain barrier (BBB), which poses significant barriers to the access of most drugs to their targets. Kynurenic acid (KYNA), a tryptophan (Trp) metabolite, plays an important role in behavioral functions, and abnormal KYNA levels have been observed in neuropsychiatric conditions. The current challenge lies in delivering KYNA to the CNS owing to its polar side chain. Recently, C-3 side chain-modified KYNA analogs have been shown to cross the BBB; however, it is unclear whether they retain the biological functions of the parent molecule. This study examined the impact of KYNA analogs, specifically, SZR-72, SZR-104, and the newly developed SZRG-21, on behavior. The analogs were administered intracerebroventricularly (i.c.v.), and their effects on the motor domain were compared with those of KYNA. Specifically, open-field (OF) and rotarod (RR) tests were employed to assess motor activity and skills. SZR-104 increased horizontal exploratory activity in the OF test at a dose of 0.04 µmol/4 µL, while SZR-72 decreased vertical activity at doses of 0.04 and 0.1 µmol/4 µL. In the RR test, however, neither KYNA nor its analogs showed any significant differences in motor skills at either dose. Side chain modification affects affective motor performance and exploratory behavior, as the results show for the first time. In this study, we showed that KYNA analogs alter emotional components such as motor-associated curiosity and emotions. Consequently, drug design necessitates the development of precise strategies to traverse the BBB while paying close attention to modifications in their effects on behavior.

Facing uncertainties: The longitudinal relationship between childhood maltreatment and exploratory behavior.

BACKGROUND: Exploratory behavior, as an essential component of decision-making, is indispensable for maximizing long-term benefits, making it a crucial factor in adolescents' psychological well-being and social adaptation. Despite the established understanding that this adaptive behavior is shaped by early adverse experiences, limited knowledge exists regarding the longitudinal relationship between childhood maltreatment and exploratory behavior. OBJECTIVE: The present study examines whether childhood maltreatment would impede subsequent exploratory behavior, considering the mediating role of uncertainty stress and the moderating role of intolerance of uncertainty. PARTICIPANTS AND SETTING: Participants were 655 adolescents from a longitudinal design with two waves spanning six months (Mage = 15.99, SDage = 0.92, 43.5 % female). METHODS: Correlation analysis and longitudinal moderated mediation effect testing were used to test our hypotheses. RESULTS: Correlation analysis indicated that childhood maltreatment was negatively correlated with exploratory behavior only simultaneously but not longitudinally. After controlling age and gender, childhood maltreatment would accompany higher levels of uncertainty stress, which in turn may act as a driving force behind subsequent exploratory behavior. The heightened intolerance of uncertainty may potentially mitigate the direct link between childhood maltreatment and later exploratory behavior. Furthermore, this trait amplifies the experienced uncertainty stress in individuals who have undergone maltreatment, thereby increasing their inclination toward engaging in subsequent exploratory behavior. CONCLUSIONS: Given the critical role of uncertainty stress, promoting more exploration among these maltreated adolescents requires corresponding cognitive and behavioral interventions to adjust their perception and cognition of uncertainty.

Alpha-Synuclein Pre-Formed Fibrils Injected into Prefrontal Cortex Primarily Spread to Cortical and Subcortical Structures.

BACKGROUND: Parkinson's disease dementia (PDD) and dementia with Lewy bodies (DLB) are characterized by diffuse spread of alpha-synuclein (α-syn) throughout the brain. Patients with PDD and DLB have a neuropsychological pattern of deficits that include executive dysfunction, such as abnormalities in planning, timing, working memory, and behavioral flexibility. The prefrontal cortex (PFC) plays a major role in normal executive function and often develops α-syn aggregates in DLB and PDD. OBJECTIVE: To investigate the long-term behavioral and cognitive consequences of α-syn pathology in the cortex and characterize pathological spread of α-syn. METHODS: We injected human α-syn pre-formed fibrils into the PFC of wild-type male mice. We then assessed the behavioral and cognitive effects between 12- and 21-months post-injection and characterized the spread of pathological α-syn in cortical, subcortical, and brainstem regions. RESULTS: We report that PFC PFFs: 1) induced α-syn aggregation in multiple cortical and subcortical regions with sparse aggregation in midbrain and brainstem nuclei; 2) did not affect interval timing or spatial learning acquisition but did mildly alter behavioral flexibility as measured by intraday reversal learning; and 3) increased open field exploration. CONCLUSIONS: This model of cortical-dominant pathology aids in our understanding of how local α-syn aggregation might impact some symptoms in PDD and DLB.

Environmental levels of azoxystrobin disturb male zebrafish behavior: Possible roles of oxidative stress, cholinergic system, and dopaminergic system.

A widely applied pesticide of azoxystrobin, is increasingly detected in the water environment. Concern has been raised against its potential detriment to aquatic ecosystems. It has been shown that exposure to azoxystrobin interfere with the locomotor behavior of zebrafish larvae. This study aims to investigate whether exposure to environmental levels of azoxystrobin (2 µg/L, 20 µg/L, and 200 µg/L) changes the behavior of male adult zebrafish. Herein, we evaluated behavioral response (locomotor, anxiety-like, and exploratory behaviors), histopathology, biochemical indicators, and gene expression in male adult zebrafish upon azoxystrobin exposure. The study showed that exposure to azoxystrobin for 42 days remarkably increased the locomotor ability of male zebrafish, resulted in anxiety-like behavior, and inhibited exploratory behavior. After treatment with 200 µg/L azoxystrobin, vasodilatation, and congestion were observed in male zebrafish brains. Exposure to 200 µg/L azoxystrobin notably elevated ROS level, MDA concentration, CAT activity, and AChE activity, while inhibiting SOD activity, GPx activity, ACh concentration, and DA concentration in male zebrafish brains. Moreover, the expression levels of genes related to the antioxidant, cholinergic, and dopaminergic systems were significantly changed. This suggests that azoxystrobin may interfere with the homeostasis of neurotransmitters by causing oxidative stress in male zebrafish brains, thus affecting the behavioral response of male zebrafish.

Specific inhibitor of Wnt/beta-catenin pathway can alter behavioral responses in young rats with malformed cortices.

The Wnt/beta-catenin pathway plays a crucial role in regulating cellular processes and has been implicated in neural activity-dependent learning as well as anxiety. However, the role of this pathway in young children with abnormal cortical development is unknown. Cortical malformations at early development, behavioral abnormalities, and a susceptibility to seizures have been reported in rats prenatally exposed to methylazoxymethanol. In this study, we aimed to investigate whether we could improve the behavioral deficits in young rats with malformed cerebral cortices by modulation of the Wnt/beta-catenin pathway. We found a small molecule Wnt/beta-catenin inhibitor (CWP) that increased exploratory behavior in the open field test (P9, CWP 100 ug treatment, peripheral exploration, P = 0.011) and social behavior test (P12, CWP 250 ug treatment, distance traveled in center, P = 0.033) and decreased anxiety in fear conditioning. However, it did not reduce the susceptibility to seizures. After high dose (250 ug) CWP treatment at P12, phosphocreatine and glutathione (GSH) were decreased in the cortex at P15 (P = 0.021). These findings suggest that the role of Wnt/beta-catenin signaling in exploratory behavior and anxiety during early development warrants further investigation.

Impact of exposure to glyphosate-based herbicide on morphological and physiological parameters in embryonic and larval development of zebrafish.

Glyphosate-based herbicides (GBH) have been commonly used in agriculture to inhibit weed growth and increase yields. However, due to the high solubility of these herbicides in water, they can reach aquatic environments, by infiltration, erosion, and/or lixiviation, affecting non target organisms. Thus, this study aimed to characterize the toxicity of GBH Roundup WG® (RWG®) during the embryonic and larval development of Danio rerio. Embryos (3 hours post fertilization, hpf-until hatching) and larvae (3 days post fertilization, dpf to 6 dpf) were exposed to concentrations of 0.065 and 6.5 mg L-1 . They were evaluated for survival, hatching, spontaneous movements, heartbeat, morphology, and morphometry by in vivo photographs in microscope, cell proliferation and apoptosis by immunohistochemistry, and exploratory behavior and phototropism by video recording. Our results showed an increase in embryo and larvae mortality in those exposed to 0.065 mg L-1 , as well as a reduction in spontaneous embryo movements. The larval heartbeats showed a decrease at 4 dpf in the group exposed to 0.065 mg L-1 and an increase at 5 and 6 dpf in both exposed groups. Cell proliferation was reduced in both groups exposed in embryos and only in the 0.065 mg L-1 group in larvae, while cell death increased in embryos exposed to 6.5 mg L-1 . These results demonstrated the toxic effect of low concentrations of the herbicide RWG® during embryonic and larval development of non target organisms, as well as the importance of constantly reviewing acceptable limits for exposure in natural environments.

Continuous high-frequency repetitive transcranial magnetic stimulation at extremely low intensity affects exploratory behavior and spatial cognition in mice.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) has been shown to be effective for cognitive intervention. However, whether HF-rTMS with extremely low intensity could influence cognitive functions is still under investigation. The present study systematically investigated the effects of continuous 40 Hz and 10 Hz rTMS on cognition in young adult mice at extremely low intensity (10 mT and 1 mT) for 11 days (30 min/day). Cognitive functions were assessed using diverse behavioral tasks, including the open field, Y-maze, and Barnes maze paradigms. We found that 40 Hz rTMS significantly impaired exploratory behavior and spatial memory in both 10 mT and 1 mT conditions. In addition, 40 Hz rTMS induced remarkably different effects on exploratory behavior between 10 mT and 1mT, compared to 10 Hz stimulation. Our results indicate that extremely low intensity rTMS can significantly alter cognitive performance depending on intensity and frequency, shedding light on the understanding of the mechanism of rTMS effects.

Rats did not show evidence of prospective information-seeking: a pilot study.

Information-seeking behavior often features in research on metacognition in non-human animals; some species seek more information when they do not know the location of a food reward. Rats are known to do this in situations of uncertainty, but it is still unclear if they seek information prospectively for solving a later problem. In this study, we investigated rats' information-seeking responses in two areas that presented different cognitive challenges (N = 4). In one area, a memory task was presented in which rats could access a cue for a food reward during the information-seeking phase of a trial, but the cue was removed before the subsequent test phase. In the other area, a discrimination task presented a cue that was available in both the information-seeking and the test phases, so that it was not necessary to seek information prospectively. The memory and discrimination test trials were given in quasi-random order (Experiment 1). Rats explored in the memory task area no more than in the discrimination task area during the information-seeking phase, even after extensive training. When they were exposed exclusively to the memory task over multiple sessions (Experiment 2), they developed a strategy of exploring the available object cues. In Experiment 3, rats were found to stay longer in an area, which had an object than in other, less potentially informative areas; they were sensitive to the presence of information. Although these results did not support the existence of prospective information-seeking in rats, they do not necessarily imply that rats lack related abilities. This consideration is due to the constraints of the small sample size and the limited scope of the testing environment. Accumulating not only positive but also negative evidence would further understanding of the factors influencing metacognitive responses in non-human animals.

A sewing needle as a urethral foreign body: A case report and literature review.

Foreign bodies in the urethra can occur by self-insertion, and patients often hide the symptoms due to embarrassment. Foreign bodies act as a focus for infection and abscess formation and result in perforation or fistula when not detected on time. Foreign bodies can display symptoms such as frequent urination, dysuria, hematuria, urethrorrhagia, and obstruction. This case discusses a self-inserted urethral sewing needle that was removed cystoscopically from an adolescent.

Late preterm and very preterm infants differ in the acquisition time and quantity of reaches with grasping at reaching onset: an exploratory study.

Introduction: The onset of manual reaching allows the expansion of the infant's interaction with the environment. When born preterm, infants become vulnerable to problems in the development of reaching. However, it is still unknown whether there are differences in reaching according to the degree of prematurity. Objective: This study aimed to explore the differences in reaching acquisition and behavior between late preterm and very preterm infants, as well as whether age and clinical variables influence the results. Method: This is an exploratory, comparative, observational study. In total, 24 infants were included soon after reaching onset; 12 infants were born late preterm (35.55 ± 0.67 gestational weeks) and 12 very preterm (30.60 ± 0.05 gestational weeks). Infants were placed in a baby seat, and a toy was placed at a reachable distance for 2 min. Reaching behavior was the primary variable; birth weight and length of hospital stay were secondary variables. Results: The age of reaching onset was higher in the very preterm group. The proportion of reaches with grasping was higher in the late preterm group. These differences were affected by the lower birth weight and longer length of hospital stay in the very preterm group. The proportions of proximal and distal adjustments did not differ between groups. Conclusion: Very preterm infants presented disadvantages in the acquisition time and the number of reaches with grasping, but not in the proportions of proximal and distal adjustments of reaching, relative to late preterm infants. Group differences were influenced by clinical variables.

Impact of the number of players on the emergence of creative movements in small-sided soccer games: a systematic review emphasizing deliberate practice.

Introduction: Creativity is a recognized quality in various areas, including sports. Within the training processes, various modifications to objectives, game configurations, rules, among other factors, can be considered to favor creative solutions to the tactical problems inherent to soccer. This systematic review aimed to identify the impact of the number of players on the emergence of creative movements in small-sided soccer games, emphasizing deliberate practice. Methods: A systematic review of Scopus, PubMed, Scielo, PsycInfo, SportDiscus and Lilacs databases was performed according to PRISMA guidelines. Eligibility criteria were defined based on the elements of population, context and concept. Only full articles published in scientific journals written in English were included. No period restriction was applied. Results: Five papers were included and the results of studies indicate greater number of actions, variability, and creativity in small-sided games compared to formal soccer matches. When comparing different small-sided game formats, 5 v 5 showed higher values in terms of total number of actions compared to 7 v 7, and the absolute number of original and creative actions tended to decrease as the game format increased. Imbalanced small-sided games format can promote increased exploratory behavior. Structural manipulation in goal positioning in 5 v 5 games may also influence the originality of tactical behaviors, while the use of different ball types in 4 v 4 games appears to decrease fluency values. In 6 v 6 games, fluency and versatility are negatively impacted. Conclusion: Reduced game formats with fewer players and in smaller field dimensions provide more suggestive environment for exploratory behavior, variability and original and creative actions. The protocol was registered on the Open Science Framework (OSF) on 2 December 2022 (DOI: 10.17605/OSF.IO/VN6YZ). Systematic review registration: [https://osf.io/jmf4k/].

An Open-Field-Based Unimodal Object Recognition Test (OF-UORT) for Assessment of Chronic Stress Effects on Visual and Tactile Unimodal Cognition in Mice.

The open field (OF) test is a widely used behavioral assay in animal studies to assess locomotion, emotion, and cognition. In open-field-based object recognition tasks, the open arena is equipped with combinations of objects to allow the examination of various aspects of learning and memory. In this article, we provide a protocol for open-field-based unimodal memory tests that assess tactile or visual unimodal cognitive behavior in mice. These tests do not require mice to be restricted from eating or drinking and do not involve aversive stimuli, such as electric shock, high-decibel sound waves, bright light, or forced swimming. Inside the apparatus, mice can freely and spontaneously explore the objects and the environment. Sniffing of, or direct contact with, objects is considered a cognitive exploration of the objects, and the timing and number of such behaviors can be recorded. During the acquisition phase, two identical objects are provided. After an intertrial interval, the retrieval phase is initiated, during which one object is replaced with a new object that is different from the previous one. Decorative clear domes are used prevent direct tactile contact with the objects, whereas infrared illumination is used to block visual information from the objects. By alternating the access to visual or tactile features of the objects in the acquisition and retrieval phases, the experimenters can assess visual or tactile unimodal cognition. Here, we describe our own instrumentation and application for experiments, and demonstrate that the modified device is capable of testing visual or tactile unimodal cognition in mice. Although easy to perform, this task/test can accurately reflect unimodal cognitive performance in mice, which can provide solid and reproducible data support to related studies. © 2023 Wiley Periodicals LLC. Basic Protocol 1: Validation of the open-field-based unimodal object recognition test Basic Protocol 2: Evaluation of chronic stress effects on unimodal cognition using the open-field-based unimodal cognitive test.

A psychiatric drug found in waste-water plant effluents alters the migratory behavior of critically endangered Anguilla anguilla juveniles.

Migratory fishes cross or settle in several environments potentially polluted. Psychiatric drugs, which represent one growing pollution and are found in discharges from waste-water treatment plants, may alter individual behaviors. Here, we assessed behavioral alterations in the upstream migratory behavior of Anguilla anguilla caused by diazepam, an anxiolytic. We monitored the swimming activity, swimming behavior, and boldness to assess whether diazepam impacts them or not. Our 7-day behavioral follow-up allowed us to test the kinetics of the potential effects of diazepam. We found diazepam reduced swimming activity and altered individual swimming behavior, with fewer individuals swimming against the current, so swimming upstream. Those effects varied over time and were stronger at the end of our monitoring, suggesting chemical pollutants encountered in estuaries may act as a chemical burden for individuals, despite metabolisation. We also found diazepam favored bolder behavior in glass eels. Our results provide new knowledge on chemical pollution and psychiatric drugs inducing behavioral alterations. Those alterations may have ecological and evolutionary consequences for glass eels, by diminishing predator avoidance and impacting spatial colonization, and thus, local density.

Calcified clumped neodymium magnetic spheres as an intravesical foreign body: case report and literature review

Foreign bodies in the bladder can occur by self-insertion, and patients often hide the symptoms owing to embarrassment. The foreign bodies act as a nidus for calculus formation when not detected for a long time. Foreign bodies can declare symptoms such as frequency, dysuria, nocturia, hematuria, urethrorrhagia, obstruction, or retention. This case spotlights self-inserted intravesical neodymium magnetic spheres clumped and calcified due to delayed presentation which were removed by open cystotomy after a cystoscopic failure.

Los cuerpos extraños en la vejiga pueden ocurrir por autoinserción y los pacientes a menudo ocultan los síntomas por vergüenza. Los cuerpos extraños actúan como un nido para la formación de cálculos cuando no se detectan durante mucho tiempo. Los cuerpos extraños pueden manifestar síntomas como polaquiuria, disuria, nicturia, hematuria, uretrorragia, obstrucción o retención. Este caso destaca esferas magnéticas de neodimio intravesicales autoinsertadas, agrupadas y calcificadas debido a una presentación tardía que se extrajeron mediante cistotomía abierta después de una falla cistoscópica.

Reproductive and neurobehavioral effects of dinotefuran in an F1 -generation toxicity study in mice.

BACKGROUND: Few studies were found for neurobehavioral toxicity of dinotefuran in mammals. This study was designed to evaluate the reproductive and neurobehavioral effects of dinotefuran exposure in mice. METHODS: Dinotefuran was given in the diet to provide levels of 0% (control), 0.015%, 0.03%, and 0.06% from 5 weeks of age of the F0 generation to 11 weeks of age of the F1 generation in mice. Selected reproductive and neurobehavioral parameters were measured. RESULTS: Movement time increased with a significant dose-related trend, and the related variables of rearing time decreased in significant dose-related trends in adult males in the F0 generation. Litter size and weight increased in significant dose-related trends, and sex ratio decreased in a significant dose-related trend. The average body weight of offspring increased in a significant dose-related trend on postnatal day (PND) 21 in both sexes. In the olfactory orientation on PND 14 in female offspring, the time required lengthened in a significant dose-related trend. In male offspring, total distance and the average speed decreased in significant dose-related trends, and the average time of rearing, number of defecations, and frequencies of mice with urination increased in a significant dose-related trend. In female offspring, the related variables of rearing increased in significant dose-related trends. In spontaneous behavior of males, the parallel lines during the control and treatment groups indicated a significant distance in the number of horizontal activities. CONCLUSIONS: The dose levels of dinotefuran in the present study produced several adverse effects on reproductive and neurobehavioral parameters in mice.

Atomoxetine promotes incentive value of modafinil and sensitizes exploratory behavior.

Substance dependence is a disorder that alters the functioning of the nervous system due to frequent abuse of drugs. The role of dopamine in the addictive effect of psychostimulants is well known; however, the involvement of the noradrenergic system is still unclear and poorly understood, though drugs like cocaine and amphetamines are known to exert significant activity on this system. The drug modafinil (MOD) has no proven addictive effect. It promotes wakefulness by acting mainly on the dopaminergic system and, to a lesser degree, the noradrenergic (NOR) system. Atomoxetine (ATX) is a non-stimulant drug that acts only on the NOR system, enhancing its activity. The aims of the present study were to analyze the effect of co-activating the DA and NOR systems (with MOD and ATX, respectively) on motor activity and exploratory behavior, and to examine the possible emergence of rewarding properties of MOD and an MOD+ATX mixture. Male Wistar rats at postnatal day 60 were treated chronically (16 days) with either monotherapy with 2ATX, 4ATX, or 60MOD mg/kg, two combinations of these substances -60MOD + 2ATX and 60MOD + 4ATX- or a vehicle. The rats co-administered with 60MOD + 4ATX reduced the rearing behavior frequency induced by MOD, but this behavior was sensitized by self-administration of the MOD+ATX mixture after chronic treatment. The rats pre-treated with 60MOD + 4ATX showed higher self-administration of MOD and greater activity on an operant task to obtain the MOD+ATX mixture. In addition, the 60MOD, 2ATX, and 60MOD + 2ATX groups showed sensitization of exploratory behavior after ingesting the mixture. Results suggest that the noradrenergic system enhances the incentive value of MOD and a MOD+ATX mixture, while also playing an important role in the sensitization of exploratory behavior.