Differences In Locomotor Activity Research Articles

The chronic cerebral hypoperfusion model induces proinflammatory cascades in Alzheimer's disease

Cerebral neuroinflammation has emerged as a significant pathway contributing to the progression of Alzheimer's disease (AD) pathology. Research implicates the NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome complex, initiating caspase 1-mediated maturation of interleukin-1 β (IL-1β) and interleukin-18 (IL-18). This study investigates whether chronic cerebral hypoperfusion (CCH), induced via permanent bilateral occlusion of the common carotid arteries (PBOCCA), leads to cognitive dysfunction and NLRP3 inflammasome activation. Twenty male Sprague Dawley (SD) rats underwent PBOCCA to induce CCH. Two weeks post-surgery, locomotor and Morris water maze (MWM) tests were conducted to examine motor functions, spatial learning, and memory, respectively. The gene expression levels of cathepsin B, NLRP3, an apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), and caspase-1 were analysed using real-time PCR, while the expression levels of the inflammatory cytokines were estimated using the ELISA method. Structural damage to the hippocampus was assessed using hematoxylin and eosin (HE) staining. Escape latencies and time spent in specific quadrants in PBOCCA significantly increased compared to sham-operated animals. There was no notable difference in locomotor activity between the PBOCCA and sham-operated groups. The number of pyknotic neurons with cytoplasmic shrinkage increased in the hippocampus. Gene expression of cathepsin B, NLRP3, ASC, and caspase-1 was upregulated in the PBOCCA group. The expression levels of IL-1β, IL-18, interleukin-6 (IL-6), and amyloid-β 1-42 (Aβ 1-42) were elevated in the PBOCCA group relative to sham. The findings confirm NLRP3 inflammasome induction, cognitive dysfunction, and inflammatory cytokines associated with AD and cerebral ischemia. The PBOCCA model provides a valuable tool for studying neurodegenerative including AD.

Neurobehavioral effects of the exposure to mercury vapor and methylmercury during postnatal period on mice.

In this study, we investigated the neurobehavioral alterations and modifications of gene expression in the brains of female mice exposed to low-level mercury vapor and/or methylmercury during postnatal development. The mice were exposed to low-level mercury vapor at a mean concentration of 0.094mg/m3 and supplied with tap water containing 5 ppm methylmercury from postnatal day 11 to 12 weeks of age. Behavioral analyses were performed at 17 weeks of age. Total locomotor activity in the open field test and the retention trial performance in the passive avoidance test were significantly reduced in the combined exposure group compared with those in the control group. The differences in locomotor activity and performance in the retention trial at 17 weeks were no longer detected at 45 weeks. These results suggest that the effect of aging on the behavioral abnormalities resulting from postnatal exposure to mercury complexes are not significant. In the microarray analysis of brains in the combined exposure group, the gene expression levels of Ano2 and Sgk1 were decreased. Real-time RT-PCR analysis confirmed these changes caused by combined mercury exposure, showing significant downregulation of Ano2 and Sgk1 in the cerebrum. These genes play key roles in the brain as a calcium-activated chloride channel and as a kinase that responds to cellular stress, respectively. Our findings provide insight into the neurobehavioral changes caused by combined mercury exposure.

Psychoactive substances 25H-NBOMe and 25H-NBOH induce antidepressant-like behavior in male rats

Ring-substituted phenethylamines are believed to induce psychedelic effects primarily by interacting with 5-hydroxytryptamine 2 (5-HT2A) receptors in the brain. We assessed the effect of the psychedelic substances 25H-NBOMe and 25H-NBOH on the depressive-like behavior of male adult rats. Naive Wistar rats were divided into groups to assess the effects of different doses (0.1 mg/kg, 1 mg/kg, and 3 mg/kg) of 25H-NBOMe and 25H-NBOH. The substances were administered intraperitoneally and the hallucinogenic properties were evaluated using the head twitch response test (HTR). Additionally, we assessed their locomotor activity in the open field test (OFT) and depressive-like behavior in the forced swimming test (FST). Our data demonstrated that all doses of synthetic psychedelic substances evaluated exhibited hallucinogenic effects. Interestingly, we observed that both 25H-NBOMe and 25H-NBOH produced a significantly greater motivation to escape in the FST, compared to the control group. Furthermore, we found no significant differences in locomotor activity during the OFT, except for the dose of 3 mg/kg, which induced a reduction in locomotion. This study provides new insights into a potential psychedelic substance, specifically by demonstrating the previously unknown antidepressant properties of a single dose of both 25H-NBOMe and 25H-NBOH. These findings contribute to the ongoing progress of experimental psychiatry toward developing safe and effective clinical practices in the field of psychedelics research.

Sex differences in long-term effects of collagen-induced arthritis in middle-aged mice.

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disorder with high prevalence among middle-aged women. Collagen-induced arthritis (CIA) is the most widely used animal model of RA, however, sex differences and long-term effects of CIA in mice are poorly described in the literature. Aim: Therefore, the present study aimed to analyze the long-term effects of CIA on the joints of middle-aged mice of both sexes and to describe potential sex differences. Materials and methods: CIA was induced in middle-aged DBA/1J mice by immunization with bovine type II collagen and complete Freund's adjuvant. Saline was administered to control mice. Arthritis score assessment, plethysmometry, and thermal imaging of the joints were performed weekly for 15weeks. Locomotor activity, micro-computed tomography, joint histology and biochemical analyses were performed at the end of the experiment. Results: Our results indicate a similar prevalence of arthritis in both sexes of mice-67% (8/12) of females and 89% (8/9) males with an earlier onset in males (day 14 vs. day 35). After the arthritis scores peaked on day 56 for males and day 63 for females, they steadily declined until the end of the experiment on day 105. A similar dynamics was observed in paw volume and temperature analyzing different aspects of joint inflammation. Long-term consequences including higher proteinuria (by 116%), loss of bone density (by 33.5%) and joint damage in terms of synovial hyperplasia as well as bone and cartilage erosions were more severe in CIA males compared to CIA females. There were no significant differences in locomotor activity between CIA mice and CTRL mice of any sex. Conclusion: This is the first study to describe the long-term effects of the CIA model in terms of sex differences in DBA/1J mice. Our results indicate sex differences in the dynamics, but not in the extent of arthritis. An earlier onset of arthritis and more severe consequences on joints, bones and kidneys were found in males. The underlying immune pathomechanisms responsible for the limited duration of the arthritis symptoms and the opposite sex difference in comparison to RA patients require further investigation.

Analysing the physical output of international field hockey players through the lens of the phase of play

The purpose of this study was to describe the locomotor activity of men's hockey based on the phase of play and to identify if differences in locomotor activity exist between phases. Twenty-four players (age 26 ± 4) wore a 10 Hz Global Positioning System device to track locomotor activity during 10 international matches. The locomotor activity of players was allocated to five different phases: (1) established attack, (2) opposition counterattack, (3) established defence, (4) attacking counterattack and (5) offensive pressing, utilising a video analysis-based system. Linear mixed models and post-hoc pairwise comparisons, using estimated marginal means, were utilised to compare the locomotor activity in each phase of play within each position. Significant main effects were found for the phase of play on several locomotor activity metrics ( p ≤ 0.05). With respect to max speed and relative total distance across positions, counterattacks present a unique challenge compared to other phases. Established attack phases evoke lower max speed values than offensive pressing phases for all playing positions as well as compared to opposition counterattacks for defenders, midfielders, and forwards. Positional differences existed during attacking counterattack phases, with defenders producing lower values than both midfielders and forwards for high-speed running, high-speed running efforts, max speed and relative total distance. Depending on the metric, this approach captured 22%–70% of a player's locomotor activity providing valuable insight into the current dynamics of international hockey. This investigation demonstrated positional differences based on the phase of play, which may explain previous research findings regarding positional differences.

Potential PTSD therapeutics targeting 5-HT<sub>2C</sub> receptors

Post-traumatic stress disorder (PTSD) is often treated by (1) selective serotonin reuptake inhibitors (SSRIs), (2) exposure therapy, or a combination of the two. However, while all treatments have some efficacy, they are not fully effective. It is necessary to elucidate the causes of inadequate efficacy and to direct the development of effective treatments. First, regarding (1), pharmacological studies have indicated that the 5-HT2C receptor is one of the receptor subtypes that interfere with the therapeutic effects of SSRIs. To compensate for nonselective effects in pharmacological manipulations, we replicated pharmacological results using mice deficient in the 5-HT2C receptor gene. However, since either pharmacological blockade or gene knockout of the 5-HT2C receptor could increase locomotor activity, the locomotor-enhancing effects make the interpretations of results difficult. Therefore, we used the conditioned lick suppression test to evaluate fear response using corrected values that consider the effects of differences in locomotor activity, thereby eliminating this possibility. Next, to address (2), we conducted fear conditioning by simultaneously presenting a composite of sound and environmental stimuli and then re-exposing the subjects to the sound and environmental stimuli separately. We found that the fear response to the sound stimuli quickly decreased, while the fear response to the environmental stimuli did not diminish even after repeated exposure. Thus, exposure therapy may exacerbate PTSD, depending on the method used. In this paper, we will introduce the above results and suggest directions for future PTSD research.

Melatonin prevented depressive-like behavior following cyclosporine A or interferon-α administration in mice

Background: Cyclosporine A (CYA) prevents graft rejection after transplantation, interferon-α (IFN-α ) is a natural cytokine prescribed in some types of malignancies and hepatitis C virus. However neurologic complication such as depression is a side effect of chronic use of these drugs. Melatonin apart from its effect on regulating the circadian rhythm, has a potent antioxidant effect and inhibits N-methyl-d-aspartic acid (NMDA) current. The goal was to evaluate the antidepressant effect of melatonin following IFN-α, and CYA administration in mice. Methods: Male NMRI mice (25-30 g) were used, IFN-α (1600000 IU/kg, sc), CYA (20 mg/kg, ip), melatonin (50 mg/kg, ip), and fluoxetine (20 mg/kg, ip) were administered daily. After evaluating the locomotor activity, depression was assessed by splash test, forced swimming test (FST), and the sucrose preference test. Results: While there was no significant difference in locomotor activity amongest different anamal groups, following melatonin pretreatment with IFN-α immobility time in FST significantly reduced (58.50±19.4s, p

Characterizing the genetic basis of trait evolution in the Mexican cavefish.

Evolution in response to a change in ecology often coincides with various morphological, physiological, and behavioral traits. For most organisms little is known about the genetic and functional relationship between evolutionarily derived traits, representing a critical gap in our understanding of adaptation. The Mexican tetra, Astyanax mexicanus, consists of largely independent populations of fish that inhabit at least 30 caves in Northeast Mexico, and a surface fish population, that inhabit the rivers of Mexico and Southern Texas. The recent application of molecular genetic approaches combined with behavioral phenotyping have established A. mexicanus as a model for studying the evolution of complex traits. Cave populations of A. mexicanus are interfertile with surface populations and have evolved numerous traits including eye degeneration, insomnia, albinism, and enhanced mechanosensory function. The interfertility of different populations from the same species provides a unique opportunity to define the genetic relationship between evolved traits and assess the co-evolution of behavioral and morphological traits with one another. To define the relationships between morphological and behavioral traits, we developed a pipeline to test individual fish for multiple traits. This pipeline confirmed differences in locomotor activity, prey capture, and startle reflex between surface and cavefish populations. To measure the relationship between traits, individual F2 hybrid fish were characterized for locomotor behavior, prey-capture behavior, startle reflex, and morphological attributes. Analysis revealed an association between body length and slower escape reflex, suggesting a trade-off between increased size and predator avoidance in cavefish. Overall, there were few associations between individual behavioral traits, or behavioral and morphological traits, suggesting independent genetic changes underlie the evolution of the measured behavioral and morphological traits. Taken together, this approach provides a novel system to identify genetic underpinnings of naturally occurring variation in morphological and behavioral traits.

Sequential delay and probability discounting tasks in mice reveal anchoring effects partially attributable to decision noise

Delay discounting and probability discounting decision making tasks in rodent models have high translational potential. However, it is unclear whether the discounted value of the large reward option is the main contributor to variability in animals’ choices in either task, which may limit translation to humans. Male and female mice underwent sessions of delay and probability discounting in sequence to assess how choice behavior adapts over experience with each task. To control for “anchoring” (persistent choices based on the initial delay or probability), mice experienced “Worsening” schedules where the large reward was offered under initially favorable conditions that became less favorable during testing, followed by “Improving” schedules where the large reward was offered under initially unfavorable conditions that improved over a session. During delay discounting, both male and female mice showed elimination of anchoring effects over training. In probability discounting, both sexes of mice continued to show some anchoring even after months of training. One possibility is that “noisy”, exploratory choices could contribute to these persistent anchoring effects, rather than constant fluctuations in value discounting. We fit choice behavior in individual animals using models that included both a value-based discounting parameter and a decision noise parameter that captured variability in choices deviating from value maximization. Changes in anchoring behavior over time were tracked by changes in both the value and decision noise parameters in delay discounting, but by the decision noise parameter in probability discounting. Exploratory decision making was also reflected in choice response times that tracked the degree of conflict caused by both uncertainty and temporal cost, but was not linked with differences in locomotor activity reflecting chamber exploration. Thus, variable discounting behavior in mice can result from changes in exploration of the decision options rather than changes in reward valuation.

Interaction between social behavior and paternal age in offspring of the same paternal mice.

AimPrevious studies reported that advanced paternal age (APA) may increase the risk of autism spectrum disorder (ASD) in offspring. However, effects of APA on behaviors have not been investigated in offspring of the same paternal mice. The present study sought to identify behavioral differences in mouse offspring of the same fathers at different paternal ages.MethodsWe assessed locomotor activity, anxiety‐like behavior, and social behavior in male mouse offspring that were born from the same fathers at three different paternal ages (3, 12, and 15 months old).ResultsNo differences in locomotor activity or anxiety‐like behavior were observed among any of the offspring groups. In the three‐chamber test, although the control group (3‐month‐old paternal age) exhibited significantly higher approach behavior toward the novel mouse compared with the novel object, the APA groups (12‐ and 15‐month‐old paternal ages) did not exhibit significant approach toward the novel mouse.ConclusionOffspring of 3‐month‐old fathers but not 12‐ or 15‐month‐old APA fathers exhibited social preference behavior. Although the present study was only exploratory, it demonstrated an interaction between social behavior and paternal age in offspring of the same paternal mice.

The Actions of Centrally Administered Nesfatin-1 on Emesis, Feeding, and Locomotor Activity in Suncus murinus (House Musk Shrew).

Nesfatin-1 is an anorectic peptide expressed in both peripheral tissues and brain areas involved in the regulation of feeding, emotion and emesis. The aim of the present study is to characterize the distribution of NUCB2/nesfatin-1 in Suncus murinus and to investigate the actions of nesfatin-1 to affect gastrointestinal contractility, emesis, food and water intake, and locomotor activity. The deduced amino acid sequence of S. murinus nesfatin-1 using in silico cloning showed high homology with humans and rodents. NUCB2 mRNA was detected throughout the entire brain and in the gastrointestinal tract, including the stomach and gut. Western blot analysis and immunohistochemistry confirmed the expression of nesfatin-1 protein in these regions. The NUCB2 mRNA levels in the hypothalamus, hippocampus and brainstem were significantly decreased, whereas that in the striatum were increased after 24 h starvation compared to ad libitum-fed animals (p < 0.05). In in vitro studies, nesfatin-1 (0.3–1,000 pM) failed to contract or relax the isolated gastric antrum and intestinal segments. In conscious, freely moving animals, intracerebroventricular administration of nesfatin-1 (1–50 pmol) induced emesis (p < 0.05) and suppressed 6-h cumulative food intake (p < 0.05), without affecting the latency to feeding. Nesfatin-1 (25 pmol, i.c.v.) decreased 24-h cumulative food and water intake by 28.3 and 35.4%, respectively (p < 0.01). No significant differences in locomotor activity were observed. In conclusion, NUCB2/nesfatin-1 might be a potent regulator of feeding and emesis in S. murinus. Further studies are required to elucidate the mechanism of actions of this peptide as a mediator linking the brainstem NUCB2/nesfatin-1 to forebrain system.

Serotonin 5-HT2C receptor knockout in mice attenuates fear responses in contextual or cued but not compound context-cue fear conditioning

Previous findings have proposed that drugs targeting 5-HT2C receptors could be promising candidates in the treatment of trauma- and stress-related disorders. However, the reduction of conditioned freezing observed in 5-HT2C receptor knock-out (KO) mice in previous studies could alternatively be accounted for by increased locomotor activity. To neutralize the confound of individual differences in locomotor activity, we measured a ratio of fear responses during versus before the presentation of a conditioned stimulus previously paired with a footshock (as a fear measure) by utilizing a conditioned licking suppression paradigm. We first confirmed that 5-HT2C receptor gene KO attenuated fear responses to distinct types of single conditioned stimuli (context or tone) independently of locomotor activity. We then assessed the effects of 5-HT2C receptor gene KO on compound fear responses by examining mice that were jointly conditioned to a context and a tone and later re-exposed separately to each. We found that separate re-exposure to individual components of a complex fear memory (i.e., context and tone) failed to elicit contextual fear extinction in both 5-HT2C receptor gene KO and wild-type mice, and also abolished differences between genotypes in tone-cued fear extinction. This study delineates a previously overlooked role of 5-HT2C receptors in conditioned fear responses, and invites caution in the future assessment of molecular targets and candidate therapies for the treatment of PTSD.

Behavioral Deficits in Adolescent Mice after Sub-Chronic Administration of NMDA during Early Stage of Postnatal Development.

Neurodevelopmental disorders are complex conditions that pose difficulty in the modulation of proper motor, sensory and cognitive function due to dysregulated neuronal development. Previous studies have reported that an imbalance in the excitation/inhibition (E/I) in the brain regulated by glutamatergic and/or GABAergic neurotransmission can cause neurodevelopmental and neuropsychiatric behavioral deficits such as autism spectrum disorder (ASD). NMDA acts as an agonist at the NMDA receptor and imitates the action of the glutamate on that receptor. NMDA however, unlike glutamate, only binds to and regulates the NMDA receptor subtypes and not the other glutamate receptors. This study seeks to determine whether NMDA administration in mice i.e., over-activation of the NMDA system would result in long-lasting behavioral deficits in the adolescent mice. Both gender mice were treated with NMDA or saline at early postnatal developmental period with significant synaptogenesis and synaptic maturation. On postnatal day 28, various behavioral experiments were conducted to assess and identify behavioral characteristics. NMDA-treated mice show social deficits, and repetitive behavior in both gender mice at adolescent periods. However, only the male mice but not female mice showed increased locomotor activity. This study implies that neonatal exposure to NMDA may illicit behavioral features similar to ASD. This study also confirms the validity of the E/I imbalance theory of ASD and that NMDA injection can be used as a pharmacologic model for ASD. Future studies may explore the mechanism behind the gender difference in locomotor activity as well as the human relevance and therapeutic significance of the present findings.

Effects of Selective Breeding, Voluntary Exercise, and Sex on Endocannabinoid Levels in the Mouse Small-Intestinal Epithelium

The endocannabinoid (eCB) system in the gut communicates with the body and brain as part of the homeostatic mechanisms that affect energy balance. Although perhaps best known for its effects on energy intake, the eCB system also regulates voluntary locomotor behavior. Here, we examined gut eCB concentrations in relation to voluntary exercise, specifically in mice selectively bred for high voluntary wheel running behavior. We measured gut eCBs in four replicate non-selected Control (C) lines and four replicate lines of High Runner (HR) mice that had been selectively bred for 74 generations based on the average number of wheel revolutions on days 5 and 6 of a 6-day period of wheel access when young adults. On average, mice from HR lines run voluntarily on wheels ∼3-fold more than C mice on a daily basis. A recent study showed that circulating levels of primary endocannabinoids 2-arachidonoyl-sn-glycerol (2-AG) and anandamide (AEA) are altered by six days of wheel access, by acute wheel running, and differ between HR and C mice in sex-specific ways [1]. We hypothesized that eCBs in the upper small-intestinal epithelium (i.e., proximal jejunum), a region firmly implicated in eCB signaling, would differ between HR and C mice (linetype), between the sexes, between mice housed with vs. without wheels for six days, and would covary with amounts of acute running and/or home-cage activity (during the previous 30 minutes). We used the same 192 mice as in [1] , half males and half females, half HR and half C (all 8 lines), and half either given or not given access to wheels for six days. We assessed the eCBs, 2-AG and AEA, and their analogs docosahexaenoylglycerol (DHG), docosahexaenoylethanolamide (DHEA), and oleoylethanolamide (OEA). Both 2-AG and DHG showed a significant 3-way interaction of linetype, wheel access, and sex. In addition, HR mice had lower concentrations of 2-AG in the small-intestinal epithelium when compared to C mice, which may be functionally related to differences in locomotor activity or to differences in body composition and/or food consumption. Moreover, the amount of home-cage activity during the prior 30 min was a negative predictor of 2-AG and AEA concentrations in jejunum mucosa, particularly in the mice with no wheel access. Lastly, 2-AG, but not AEA, was significantly correlated with 2-AG in plasma in the same mice.

The influence of estrogen receptor α signaling independent of the estrogen response element on avoidance behavior, social interactions, and palatable ingestive behavior in female mice

Women are vulnerable to developing mental disorders that are associated with circulating estrogens. Estrogens, especially 17β-estradiol (E2), have a wide array of effects on the brain, affecting many behavioral endpoints associated with mental illness. By using a total estrogen receptor (ER) α knockout (KO), an ERα knock in/knock out (KIKO) that lacks a functional DNA-binding domain, and wild type (WT) controls treated with either oil or E2, we evaluated ERα signaling, dependent and independent of the estrogen response element (ERE), on avoidance behavior, social interactions and memory, and palatable ingestive behavior using the open field test, the elevated plus maze, the light dark box, the 3-chamber test, and palatable feeding. We found that ERα does not mediate control of anxiety-like behaviors but rather yielded differences in locomotor activity. In evaluating social preference and social recognition memory, we observed that E2 may modulate these measures in KIKO females but not KO females, suggesting that ERE-independent signaling is likely involved in sociability. Lastly, observations of palatable (high-fat) food intake suggested an increase in palatable eating behavior in oil-treated KIKO females. Oil-treated KO females had a longer latency to food intake, indicative of an anhedonic phenotype compared to oil-treated WT and KIKO females. We have observed that social-related behaviors are potentially influenced by ERE-independent ERα signaling and hedonic food intake requires signaling of ERα.

Effects of fentanyl on acute locomotor activity, behavioral sensitization, and contextual reward in female and male rats

BackgroundAlthough fentanyl has gained widespread prominence, there remains a lack of knowledge on this opioid synthetic agonist, particularly related to sex effects. Therefore, we conducted behavioral tests in female and male rats to measure drug abuse-related responses to fentanyl hypothesizing sex-specific responses. MethodsUsing female and male rats, we measured the effects of acute or repeated administration of fentanyl (20 μg/kg) on locomotor activity (LMA) and behavioral sensitization in an open field test. We further measured contextual-reward and associated locomotor activity during training in a conditioned place preference (CPP) paradigm using a low (4 μg/kg) or high (16 μg/kg) dose of fentanyl. Vaginal lavage samples were collected from female rats in the CPP study, and the estrous phase was determined based on the cytological characterization. ResultsFemale, but not male, rats showed elevated LMA in response to acute fentanyl and behavioral sensitization to repeated administration of fentanyl. Fentanyl produced significant CPP in both sexes, but it was more potent in males. Finally, our secondary investigation of the estrous cycle on fentanyl-CPP suggests that non-estrus phases, likely reflecting high estradiol, may predict the degree of fentanyl preference in females. ConclusionsFentanyl was more potent and/or effective to produce LMA and LMA sensitization in females but more potent to produce CPP in males. Furthermore, the role of sex in fentanyl responses varied across endpoints, and sex differences in LMA were not predictive of sex differences in CPP.

Comparison of mouse models reveals a molecular distinction between psychotic illness in PWS and schizophrenia

Prader-Willi Syndrome (PWS) is a neurodevelopmental disorder caused by mutations affecting paternal chromosome 15q11-q13, and characterized by hypotonia, hyperphagia, impaired cognition, and behavioural problems. Psychotic illness is a challenging problem for individuals with PWS and has different rates of prevalence in distinct PWS genotypes. Previously, we demonstrated behavioural and cognitive endophenotypes of relevance to psychiatric illness in a mouse model for one of the associated PWS genotypes, namely PWS-IC, in which deletion of the imprinting centre leads to loss of paternally imprinted gene expression and over-expression of Ube3a. Here we examine the broader gene expression changes that are specific to the psychiatric endophenotypes seen in this model. To do this we compared the brain transcriptomic profile of the PWS-IC mouse to the PWS-cr model that carries a deletion of the PWS minimal critical interval spanning the snoRNA Snord116 and Ipw. Firstly, we examined the same behavioural and cognitive endophenotypes of relevance to psychiatric illness in the PWS-cr mice. Unlike the PWS-IC mice, PWS-cr exhibit no differences in locomotor activity, sensory-motor gating, and attention. RNA-seq analysis of neonatal whole brain tissue revealed a greater number of transcriptional changes between PWS-IC and wild-type littermates than between PWS-cr and wild-type littermates. Moreover, the differentially expressed genes in the PWS-IC brain were enriched for GWAS variants of episodes of psychotic illness but, interestingly, not schizophrenia. These data illustrate the molecular pathways that may underpin psychotic illness in PWS and have implications for potential therapeutic interventions.

Mood Regulatory Actions of Active and Sham Nucleus Accumbens Deep Brain Stimulation in Antidepressant Resistant Rats.

The antidepressant actions of deep brain stimulation (DBS) are associated with progressive neuroadaptations within the mood network, modulated in part, by neurotrophic mechanisms. We investigated the antidepressant-like effects of chronic nucleus accumbens (NAc) DBS and its association with change in glycogen synthase kinase 3 (GSK3) and mammalian target of rapamycin (mTOR) expression in the infralimbic cortex (IL), and the dorsal (dHIP) and ventral (vHIP) subregions of the hippocampus of antidepressant resistant rats. Antidepressant resistance was induced via daily injection of adrenocorticotropic hormone (ACTH; 100 μg/day; 15 days) and confirmed by non-response to tricyclic antidepressant treatment (imipramine, 10 mg/kg). Portable microdevices provided continuous bilateral NAc DBS (130 Hz, 200 μA, 90 μs) for 7 days. A control sham electrode group was included, together with ACTH- and saline-treated control groups. Home cage monitoring, open field, sucrose preference, and, forced swim behavioral tests were performed. Post-mortem levels of GSK3 and mTOR, total and phosphorylated, were determined with Western blot. As previously reported, ACTH treatment blocked the immobility-reducing effects of imipramine in the forced swim test. In contrast, treatment with either active DBS or sham electrode placement in the NAc significantly reduced forced swim immobility time in ACTH-treated animals. This was associated with increased homecage activity in the DBS and sham groups relative to ACTH and saline groups, however, no differences in locomotor activity were observed in the open field test, nor were any group differences seen for sucrose consumption across groups. The antidepressant-like actions of NAc DBS and sham electrode placements were associated with an increase in levels of IL and vHIP phospho-GSK3β and phospho-mTOR, however, no differences in these protein levels were observed in the dHIP region. These data suggest that early response to electrode placement in the NAc, irrespective of whether active DBS or sham, has antidepressant-like effects in the ACTH-model of antidepressant resistance associated with distal upregulation of phospho-GSK3β and phospho-mTOR in the IL and vHIP regions of the mood network.

Modification of the Daily Activity Pattern of the Diurnal Triatomine Mepraia spinolai (Hemiptera: Reduviidae) Induced by Trypanosoma cruzi (Trypanosomatida: Trypanosomatidae) Infection.

Mepraia spinolai, (Porter) 1934, is a diurnal triatomine endemic to Chile and a wild vector of the protozoan Trypanosoma cruzi, (Chagas) 1909, which causes Chagas disease. Behavioral changes in M. spinolai induced by this parasite have been reported previously, which include detection of a potential host, defecation latency, and some life history traits. In this study we assessed changes in locomotor and daily activity due to infection with T. cruzi. No difference was detected in distance traveled between infected and uninfected individuals. However, the groups differed in their daily activity patterns; infected individuals showed significant reduction of movements during the light phase and concentrated their activity in the dark phase. Uninfected individuals showed no differences in locomotor activity between the phases. The results suggest that T. cruzi induces a displacement in the activity of M. spinolai toward the dark phase of the circadian cycle, which may improve its vector competence.

Correlation between ketones and mental fatigue in high fat-induced obese and non-obese rats.

Obesity, often caused by a diet high in calories and low physical activity, may induce physical fatigue, as experienced via decreased locomotor activity and mental fatigue such as impaired cognition. This study aims to evaluate glucose and ketone levels secondary to high‐fat diet (HFD) exposure and signs of physical and mental fatigue. Fifty‐four 7‐week‐old male Sprague Dawley rats (Rattus norvegicus) were assigned to either an HFD (n = 28) or a standard diet (SD; n = 26) for a 6‐week period during which body weight, blood glucose, and ketones were measured twice per week. An open field (OF) paradigm was used to measure locomotor activity, while novel object recognition (NOR) test was used as an indicator of cognition. Animals in the HFD group weighed more than SD rats (8.4 g; p < 0.05) starting at Day 11, blood glucose levels were higher in the HFD group versus SD rats (3.9 mg/dl; p < 0.05) beginning in Week 5, and ketones were lower for the HFD versus the SD group throughout the study (0.34 mmol/L on average; p < 0.05). Although there was no significant difference in locomotor activity between the HFD and SD groups (p = 0.12), regardless of diet, higher ketone levels were associated with increased NOR time and ratio between the familiar and novel objects (p < 0.01). Thus, this study provides evidence that an increased level of ketones is associated with greater cognitive performance and a lesser probability of experiencing mental fatigue.