Behavioral Changes In Rodents Research Articles

Differences in Fluid, Electrolyte, and Energy Balance in C57BL/6J Mice (Mus musculus) in Metabolic Caging at Thermoneutral or Standard Room Temperatures.

The Guide for the Care and Use of Laboratory Animals recommends mice be pair or group housed and provided with nesting materials. These provisions support social interactions and are also critical for thermoregulatory behaviors such as huddling and burrowing. However, studies of fluid and electrolyte balance and digestive function may involve use of metabolic caging (MC) systems in which mice are housed individually on wire-mesh floors that permit quantitative collection of urine and feces. MC housing prevents mice from performing their typical huddling and burrowing behaviors. Housing in MC can cause weight loss and behavioral changes in rodents. Here, we tested the hypothesis that MC housing of mice at standard room temperature (SRT, 22 to 23 °C) exposes them to cold stress, which causes metabolic changes in the mice as compared with standard housing. We hypothesized that performing MC studies at a thermoneutral temperature (TNT, 30 °C) would minimize these changes. Fluid, electrolyte, and energy balance and body composition were assessed in male and female C57BL/6J mice housed at SRT or TNT in MC, static microisolation cages, or a multiplexed metabolic phenotyping system designed to mimic static microisolation cages (Promethion, Sable Systems International). In brief, as compared with MC housing at SRT, MC housing at TNT was associated with lower food intake and energy expenditure, absence of weight loss, and lower urine and fecal corticosterone levels. These results indicate that housing in MC at SRT causes cold stress that can be mitigated if MC studies are performed at TNT.

Antibiotic-induced gut dysbiosis and cognitive, emotional, and behavioral changes in rodents: a systematic review and meta-analysis.

There are previous epidemiological studies reporting associations between antibiotic use and psychiatric symptoms. Antibiotic-induced gut dysbiosis and alteration of microbiota-gut-brain axis communication has been proposed to play a role in this association. In this systematic review and meta-analysis, we reviewed published articles that have presented results on changes in cognition, emotion, and behavior in rodents (rats and mice) after antibiotic-induced gut dysbiosis. We searched three databases-PubMed, Web of Science, and SCOPUS to identify such articles using dedicated search strings and extracted data from 48 articles. Increase in anxiety and depression-like behavior was reported in 32.7 and 40.7 percent of the study-populations, respectively. Decrease in sociability, social novelty preference, recognition memory and spatial cognition was found in 18.1, 35.3, 26.1, and 62.5 percent of the study-populations, respectively. Only one bacterial taxon (increase in gut Proteobacteria) showed statistically significant association with behavioral changes (increase in anxiety). There were no consistent findings with statistical significance for the potential biomarkers [Brain-derived neurotrophic factor (BDNF) expression in the hippocampus, serum corticosterone and circulating IL-6 and IL-1β levels]. Results of the meta-analysis revealed a significant association between symptoms of negative valence system (including anxiety and depression) and cognitive system (decreased spatial cognition) with antibiotic intake (p < 0.05). However, between-study heterogeneity and publication bias were statistically significant (p < 0.05). Risk of bias was evaluated to be high in the majority of the studies. We identified and discussed several reasons that could contribute to the heterogeneity between the results of the studies examined. The results of the meta-analysis provide promising evidence that there is indeed an association between antibiotic-induced gut dysbiosis and psychopathologies. However, inconsistencies in the implemented methodologies make generalizing these results difficult. Gut microbiota depletion using antibiotics may be a useful strategy to evaluate if and how gut microbes influence cognition, emotion, and behavior, but the heterogeneity in methodologies used precludes any definitive interpretations for a translational impact on clinical practice.

The use of chemogenetic actuator ligands in nonhuman primate DREADDs-fMRI.

Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) are engineered receptors that allow for genetically targeted, reversible manipulation of cellular activity via systemic drug administration. DREADD induced manipulations are initiated via the binding of an actuator ligand. Therefore, the use of DREADDs is contingent on the availability of actuator ligands. Actuator ligands low-dose clozapine (CLZ) and deschloroclozapine (DCZ) are highly selective for DREADDs, and, upon binding, induce physiological and behavioral changes in rodents and nonhuman primates (NHPs). Despite this reported specificity, both CLZ and DCZ have partial affinity for a variety of endogenous receptors and can induce dose-specific changes even in naïve animals. As such, this study aimed to examine the effects of CLZ and DCZ on resting-state functional connectivity (rs-FC) and intrinsic neural timescales (INTs) in naïve NHPs. In doing so, we evaluated whether CLZ and DCZ - in the absence of DREADDs - are inert by examining these ligands' effects on the intrinsic functional properties of the brain. Low-dose DCZ did not induce consistent changes in rs-FC or INTs prior to the expression of DREADDs; however, a high dose resulted in subject-specific changes in rs-FC and INTs. In contrast, CLZ administration induced consistent changes in rs-FC and INTs prior to DREADD expression in our subjects. Our results caution against the use of CLZ by explicitly demonstrating the impact of off-target effects that can confound experimental results. Altogether, these data endorse the use of low dose DCZ for future DREADD-based experiments.

Social effects of rabies infection in male vampire bats (Desmodus rotundus).

Rabies virus (RABV) transmitted by the common vampire bat (Desmodus rotundus) poses a threat to agricultural development and public health throughout the Neotropics. The ecology and evolution of rabies host-pathogen dynamics are influenced by two infection-induced behavioural changes. RABV-infected hosts often exhibit increased aggression which facilitates transmission, and rabies also leads to reduced activity and paralysis prior to death. Although several studies document rabies-induced behavioural changes in rodents and other dead-end hosts, surprisingly few studies have measured these changes in vampire bats, the key natural reservoir throughout Latin America. Taking advantage of an experiment designed to test an oral rabies vaccine in captive male vampire bats, we quantify for the first time, to our knowledge, how rabies affects allogrooming and aggressive behaviours in this species. Compared to non-rabid vampire bats, rabid individuals reduced their allogrooming prior to death, but we did not detect increases in aggression among bats. To put our results in context, we review what is known and what remains unclear about behavioural changes of rabid vampire bats (resumen en español, electronic supplementary material, S1).

Behavioral Changes Induced by Latent Toxoplasmosis Could Arise from CNS Inflammation and Neuropathogenesis.

Chronic infection with Toxoplasma gondii, a neurotropic parasite, has been linked to multiple behavioral changes in rodents and humans. The pathogenic mechanisms underlying these correlations are not known. I discuss here from animal studies the distribution of tissue cysts, the constant immune surveillance, the critical role of cyst burden, and the time-dependent consequences, which I believe are crucial to explaining the behavioral changes. In line with the brain-wide distribution of tissue cysts and chronic neuroinflammation, infected mice displayed a broad range of behavioral phenotypes. Many studies suggest that behavioral changes in mice are directly associated with tissue cyst presence or cyst burden and the host immune response. Cyst burden may not exert direct effects; however, the mechanisms causing behavioral and neuropathological changes are potentially the consequence of cyst burden over time, such as the neuroinflammation required to control the reactivation of tissue cysts. The reduction of neuroinflammation has proven that neuropathogenesis and behavioral abnormalities can be reversed, at least partially, in infected mice. Overall, Toxoplasma-induced behavioral changes are likely to be an indirect consequence of the host immune response in a parasite burden-dependent manner.

Neuroinflammatory process in animals infected by Toxoplasma gondii: an integrative review

Toxoplasma gondii (T. gondii) is a eurixene parasite, of which felines are the definitive hosts and other warm-blooded animals, the intermediate hosts, having clinical importance mainly in immunocompromised individuals, which can cause behavioral changes in rodents. Among the neurophysiological mechanisms used to explain this phenomenon, there is the influence of the immune response on the central nervous system (CNS). Since neuroimmunology has been gaining ground in science in the recent years, the aim of this article was to assess the approaches in the current literature on the neuroinflammatory process in an animal model infected with T. gondii, making use of an integrative literature review. Articles indexed in the PubMed and Scopus databases that met the inclusion criteria and that carried out experimental research with rodents from January 2012 to February 2022 were considered. Forty-two articles were found, of which 18 were selected for full reading and 24 were excluded. The approaches evaluated were: a) correlation between physical state or animal behavior and neuroinflammation; b) influence of astrocytes, microglia, and neurons in the neuroinflammatory process; c) influence of the immune response to changes in neurotransmitters; and d) other immunological factors and their influence on the CNS. The integrative review allowed the discussion of the main approaches in the literature on the subject, giving an overview, in which some considerations were made that may contribute to the development of new experimental research, in order to assess the influence of the immune response on the CNS of parasitized animals.

A functional selective effect of oxytocin secreted under restraint stress in rats

Restraint stress (RS) is an unavoidable stress model that triggers activation of the autonomic nervous system, endocrine activity, and behavioral changes in rodents. Furthermore, RS induces secretion of oxytocin into the bloodstream, indicating a possible physiological role in the stress response in this model. The presence of oxytocin receptors in vessels and heart favors this possible idea. However, the role of oxytocin secreted in RS and effects on the cardiovascular system are still unclear. The aim of this study was to analyze the influence of oxytocin on cardiovascular effects during RS sessions. Rats were subjected to pharmacological (blockade of either oxytocin, vasopressin, or muscarinic receptors) or surgical (hypophysectomy or sinoaortic denervation) approaches to study the functional role of oxytocin and its receptor during RS. Plasma levels of oxytocin and vasopressin were measured after RS. RS increased arterial pressure, heart rate, and plasma oxytocin content, but not vasopressin. Treatment with atosiban (a Gi biased agonist) inhibited restraint-evoked tachycardia without affecting blood pressure. However, this effect was no longer observed after sinoaortic denervation, homatropine (M2 muscarinic antagonist) treatment or hypophysectomy, indicating that parasympathetic activation mediated by oxytocin secreted to the periphery is responsible for blocking the increase in tachycardic responses observed in the atosiban-treated group. Corroborating this, L-368,899 (oxytocin antagonist) treatment showed an opposite effect to atosiban, increasing tachycardic responses to restraint. Thus, this provides evidence that oxytocin secreted to the periphery attenuates tachycardic responses evoked by restraint via increased parasympathetic activity, promoting cardioprotection by reducing the stress-evoked heart rate increase.

Peripheral Taenia infection increases immunoglobulins in the central nervous system

Human cysticercosis is a disease caused by larvae of the cestode Taenia solium. It is an important common cause of adult-onset seizures world-wide where it exacts a debilitating toll on the health and well-being of affected communities. It is commonly assumed that the major symptoms associated with cysticercosis are a result of the direct presence of larvae in the brain. As a result, the possible effects of peripherally located larvae on the central nervous system are not well understood. To address this question, we utilised the Taenia crassiceps intra-peritoneal murine model of cysticercosis, where larvae are restricted to the peritoneal cavity. In this model, previous research has observed behavioural changes in rodents but not the development of seizures. Here we used ELISAs, immunoblotting and the Evans Blue test for blood–brain barrier permeability to explore the central effects of peripheral infection of mice with T. crassiceps. We identified high levels of parasite-targeting immunoglobulins in the sera of T. crassiceps-infected mice. We show that the T. crassciceps larvae themselves also contain and release host immunoglobulins over time. Additionally, we describe, for the first known time, significantly increased levels of IgG within the hippocampi of infected mice, which are accompanied by changes in blood–brain barrier permeability. However, these T. crassiceps-induced changes were not accompanied by alterations to the levels of proinflammatory, pro-seizure cytokines in the hippocampus. These findings contribute to the understanding of systemic and neuroimmune responses in the T. crassiceps model of cysticercosis, with implications for the pathogenesis of human cysticercosis.

Serum Tyrosine Level in Acute Murine Toxoplasmosis.

Background:Toxoplasmosis is a zoonotic disease caused by the obligate intracellular parasite, Toxoplasma gondii. This global infectious disease has been associated with behavioral changes in rodents and can result in humans’ neuropsychiatric symptoms. Since the neurotransmitters alteration can cause a behavioral change, in this study, tyrosine level, as a precursor of dopamine, was evaluated in acute murine toxoplasmosis during 2015 and 2016 in Shiraz, Iran.Methods:At the first, 105 tachyzoites of T. gondii were subcutaneously inoculated to 50 BALB/c mice as experimental groups and 10 mice inoculated by PBS considered as the control group. After that, daily, one group of mice was bled, and sera were collected. Then, their serum tyrosine level was evaluated by HPLC method.Results:After data analysis, the maximum mean serum tyrosine level was seen at 2th day of post parasite inoculation (0.0194 mg/ ml), with a significant difference compared to the control group (0.0117 mg/ ml, P=0.025). Moreover, the least quantity of serum tyrosine (0.076 mg/ml) was seen on the 5th day, after parasite inoculation, however, no significant difference was seen.Conclusion:Serum tyrosine level increased in 2 d after inoculation of Toxoplasma, but the level regularly decreased in successive days. Tyrosine level increased by phenylalanine hydroxylase 2 days after inoculation, then tyrosine decreased by tyrosine hydroxylase in the next days. Toxoplasma tyrosine hydroxylase enzymes, at primary days of toxoplasmosis, effect on tyrosine production, and after that, the most effect on tyrosine consumption.

Roles of Toll-like receptor 2/4, monoacylglycerol lipase, and cyclooxygenase in social defeat stress-induced prostaglandin E2 synthesis in the brain and their behavioral relevance

Inflammation in the brain and periphery has been associated with stress-related pathology of mental illness. We have shown that prostaglandin (PG) E2, an arachidonic acid-derived lipid mediator, and innate immune receptors Toll-like receptor (TLR) 2/4 are crucial for repeated stress-induced behavioral changes in rodents. However, how the stress induces PGE2 synthesis in the brain and whether TLR2/4 are involved in the PGE2 synthesis remain unknown. Using mice lacking TLR2 and TLR4 in combination, here we show that social defeat stress (SDS) induced the PGE2 synthesis in subcortical, but not cortical, tissues in a TLR2/4-dependent manner. It is known that PGE2 in the brain is mainly derived by monoacylglycerol lipase (MAGL)-mediated conversion of endocannabinoid 2-arachidonoylglycerol to free-arachidonic acid, a substrate for cyclooxygenase (COX) for PGE2 synthesis. We found that TLR2/4 deletion reduced the mRNA expression of MAGL and COX1 in subcortical tissues after repeated SDS. Perturbation of MAGL and COX1 as well as COX2 abolished SDS-induced PGE2 synthesis in subcortical tissues. Furthermore, systemic administration of JZL184, an MAGL inhibitor, abolished repeated SDS-induced social avoidance. These results suggest that SDS induces PGE2 synthesis in subcortical regions of the brain via the MAGL-COX pathway in a TLR2/4-dependent manner, thereby leading to social avoidance.

Guanabenz Reverses a Key Behavioral Change Caused by Latent Toxoplasmosis in Mice by Reducing Neuroinflammation.

Toxoplasma gondii is an intracellular parasite that has infected one-third of humans. The infection is permanent because the replicative form (tachyzoite) converts into a latent tissue cyst form (bradyzoite) that evades host immunity and is impervious to current drugs. The continued presence of these parasitic cysts hinders treatment and leads to chronic infection that has been linked to behavioral changes in rodents and neurological disease in humans. How these behavioral changes occur, and whether they are due to parasite manipulation or the host response to infection, remains an outstanding question. We previously showed that guanabenz possesses antiparasitic activity; here, we show that guanabenz reproducibly lowers brain cyst burden up to 80% in chronically infected male and female BALB/cJ mice when given intraperitoneally but not when administered by gavage or in food. Regardless of the administration route, guanabenz reverses Toxoplasma-induced hyperactivity in latently infected mice. In contrast, guanabenz increases cyst burden when given to chronically infected C57BL/6J mice yet still reverses Toxoplasma-induced hyperactivity. Examination of the brains from chronically infected BALB/cJ and C57BL/6J mice shows that guanabenz decreases inflammation and perivascular cuffing in each strain. Our study establishes a robust model for cyst reduction in BALB/cJ mice and shows for the first time that it is possible to reverse a key behavioral change associated with latent toxoplasmosis. The rescue from parasite-induced hyperactivity correlates with a decrease in neuroinflammation rather than reduced cyst counts, suggesting that some behavioral changes arise from host responses to infection.IMPORTANCEToxoplasma gondii is a common parasite of animals, including up to one-third of humans. The single-celled parasite persists within hosts for the duration of their life as tissue cysts, giving rise to chronic infection. Latent toxoplasmosis is correlated with neurological dysfunction in humans and results in dramatic behavioral changes in rodents. When infected, mice and rats adapt behaviors that make them more likely to be devoured by cats, the only host that supports the sexual stage of the parasite. In this study, we establish a new mouse model of tissue cyst depletion using a drug called guanabenz and show that it is possible to reverse a key behavior change back to normal in infected animals. We also show that the mechanism appears to have nothing to do with parasite cyst burden but rather the degree of neuroinflammation produced by chronic infection.

Effects of Maternal Deprivation on Anxiety, Depression, and Empathy in Male and Female Offspring of Wistar Rats in the Face of Novel Objects.

Background: Early life stress (ELS) models such as maternal deprivation (MD) are used to investigate behavioral changes in rodents under stressful situations. MD is a situation in which rat pups are separated from the dam; MD has different paradigms. The purpose of this research is to evaluate the effects of maternal deprivation on anxiety, depression, and empathy in adult Wistar rats. Materials and Methods: MD was applied to pups as per specifically designed protocol to compare rats of the control group with maternal deprivation rats and also the group, which faced novel objects. Each group consisted of eight rats. In this study, separation started from postnatal day (PND) 14 for various periods up to PND 60. EPM test was undertaken to measure anxiety; moreover, FST was used to indicate levels of depression. Also, changes in the empathy ratio were also demonstrated. One-way analysis of variance (ANOVA), Tukey’s post hoc analysis, and t-test were applied to analyze the results. Results: MD-treated rats showed a significant decrease in anxiety and empathy indexes compared with those in the control group (P<0.05). However, MD significantly increased depression in both male and female rats (P<0.05). Finally, exposure to novel objects decreased depression but did not have any effect on anxiety and empathy levels in MD rats (P<0.05). Conclusion: ELS may lead to various states of mood and behavior in adulthood. According to the findings of this study, depression increases due to MD, though both anxiety and empathy decrease in both male and female Wistar rats. Moreover, exposure to novel objects decreases depression, while anxiety and empathy do not change significantly with exposure to novel objects.

Effects of Maternal Deprivation on Anxiety, Depression, and Empathy in Male and Female Offspring of Wistar Rats in the Face of Novel Objects

Background: Early life stress (ELS) models such as maternal deprivation (MD) are used to in¬vestigate behavioral changes in rodents under stressful situations. MD is a situation in which rat pups are separated from the dam; MD has different paradigms. The purpose of this research is to evaluate the effects of maternal deprivation on anxiety, depression, and empathy in adult Wistar rats. Materials and Methods: MD was applied to pups as per specifically designed protocol to compare rats of the control group with maternal deprivation rats and also the group, which faced novel objects. Each group consisted of eight rats. In this study, separation started from postnatal day (PND) 14 for various periods up to PND 60. EPM test was undertaken to measure anxiety; moreover, FST was used to indicate levels of depression. Also, changes in the empathy ratio were also demonstrated. One-way analysis of variance (ANOVA), Tukey’s post hoc analysis, and t-test were applied to analyze the results. Results: MD-treated rats showed a significant decrease in anxiety and empathy indexes compared with those in the control group (P&lt;0.05). However, MD significantly increased depression in both male and female rats (P&lt;0.05). Final¬ly, exposure to novel objects decreased depression but did not have any effect on anxiety and empathy levels in MD rats (P&lt;0.05). Conclusion: ELS may lead to various states of mood and behavior in adulthood. According to the findings of this study, depression increases due to MD, though both anxiety and empathy decrease in both male and female Wistar rats. Moreover, ex¬posure to novel objects decreases depression, while anxiety and empathy do not change signifi¬cantly with exposure to novel objects. [GMJ.2019;8:e1093]

Effects of Maternal Deprivation on Anxiety, Depression, and Empathy in Male and Female Offspring of Wistar Rats in the Face of Novel Objects

Background: Early life stress (ELS) models such as maternal deprivation (MD) are used to in¬vestigate behavioral changes in rodents under stressful situations. MD is a situation in which rat pups are separated from the dam; MD has different paradigms. The purpose of this research is to evaluate the effects of maternal deprivation on anxiety, depression, and empathy in adult Wistar rats. Materials and Methods: MD was applied to pups as per specifically designed protocol to compare rats of the control group with maternal deprivation rats and also the group, which faced novel objects. Each group consisted of eight rats. In this study, separation started from postnatal day (PND) 14 for various periods up to PND 60. EPM test was undertaken to measure anxiety; moreover, FST was used to indicate levels of depression. Also, changes in the empathy ratio were also demonstrated. One-way analysis of variance (ANOVA), Tukey’s post hoc analysis, and t-test were applied to analyze the results. Results: MD-treated rats showed a significant decrease in anxiety and empathy indexes compared with those in the control group (P&lt;0.05). However, MD significantly increased depression in both male and female rats (P&lt;0.05). Final¬ly, exposure to novel objects decreased depression but did not have any effect on anxiety and empathy levels in MD rats (P&lt;0.05). Conclusion: ELS may lead to various states of mood and behavior in adulthood. According to the findings of this study, depression increases due to MD, though both anxiety and empathy decrease in both male and female Wistar rats. Moreover, ex¬posure to novel objects decreases depression, while anxiety and empathy do not change signifi¬cantly with exposure to novel objects. [GMJ.2019;8:e1093]

Alteration of oxidative stress markers and behavior of rats in a novel model of depression

Emotional stress is considered a serious pathogenetic factor of depression. In this study an ultrasound model of emotional stress developed in our laboratory was applied. It is characterized by the use of ultrasound as the stressor agent. Animals are triggered not by any organic or physical disturbances but by the perception of adverse information. This type of stress can induce depressive-like behavioral changes in rodents, manifested by decreased sucrose preference and increased time of immobility in a forced swim test. Ultrasound stress also increased the levels of oxidative stress markers. This is important, as stress has an established association with increased oxidative processes in the central nervous system. Total glutathione and carbonyl protein content were selected as relevant brain markers, as glutathione plays a critical role in cellular defensive mechanisms during oxidative stress and the level of protein carbonyls can be a measure of global protein oxidation. We demonstrated that two weeks of chronic exposure to ultrasound was enough to cause depressive-like behavioral changes in rats. Increased levels of oxidative stress markers in the hippocampus and prefrontal cortex were also observed after two weeks of such stress. The current study has two goals: the first is to study the relationship of depression and oxidative stress; the second is an additional validation of our approach to modeling stress‑induced depressive-like states in rats. The present data further support the validity of the ultrasound model by expanding information related to the influence of ultrasound stress on behavioral and physiological parameters, which are of great importance in the development of stress-induced depression. A time correlation between the onset of symptoms and a change in the level of oxidative stress markers in the brain is also demonstrated.

Behavioral evaluation of BALB/c (Mus musculus) mice infected with genetically distinct strains of Toxoplasma gondii

In relation to behavioral changes in rodents infected with Toxoplasma gondii (T. gondii), it is believed that the genotype of the infecting strain can have some influence. In this sense, the present work has sought to evaluate the effect of chronic infection by genetically distinct cystogenic strains of T. gondii on the behavior of mice. For this, experimental models of infection with ME-49 (type II) and VEG (type III) strains were developed in isogenic BALB/c mice. ELISA test was performed to evaluate the humoral immune response and real-time PCR test to quantify parasites in the CNS. Behavioral tests such as passive avoidance, open-field and Y-maze tests were also used for, respectively, evaluation of learning and memory, locomotor activity and aversion to feline odor. The results showed that mice infected with VEG strain had higher total IgG level of anti-toxoplasma, higher tissue burden of T. gondii in the CNS, reduction in the long-term memory, lower activity (mobility) and lower aversion to cat urine and l-felinine than mice infected with ME-49 strain. The results suggest that different T. gondii genotypes have a differential impact on behavioral changes in infected mice.

Impairment of Long-Term Plasticity of Cerebellar Purkinje Cells Eliminates the Effect of Anodal Direct Current Stimulation on Vestibulo-Ocular Reflex Habituation.

Anodal direct current stimulation (DCS) of the cerebellum facilitates adaptation tasks, but the mechanism underlying this effect is poorly understood. We have evaluated whether the effects of DCS effects depend on plasticity of cerebellar Purkinje cells (PCs). Here, we have successfully developed a mouse model of cerebellar DCS, allowing us to present the first demonstration of cerebellar DCS driven behavioral changes in rodents. We have utilized a simple gain down vestibulo-ocular reflex (VOR) adaptation paradigm, that stabilizes a visual image on the retina during brief head movements, as behavioral tool. Our results provide evidence that anodal stimulation has an acute post-stimulation effect on baseline gain reduction of VOR (VOR gain in sham, anodal and cathodal groups are 0.75 ± 0.12, 0.68 ± 0.1, and 0.78 ± 0.05, respectively). Moreover, this anodal induced decrease in VOR gain is directly dependent on the PP2B medicated synaptic long-term potentiation (LTP) and intrinsic plasticity pathways of PCs.

SA79. Toxoplasma Gondii Affects Posterior Association Cortex and Related Functions in Healthy, but Not Schizophrenia, Individuals

Abstract Background: The apicomplexan protozoa Toxoplasma gondii (TG) is a successful parasite infecting ~30% of the human population, with some evidence to suggest it is more frequent in individuals with schizophrenia. TG has an affinity for the central nervous system and has been linked to cognitive and behavioral changes in rodents as well as humans. It is believed this mechanism contributes to the presentation of some schizophrenia cases. Given the relative absence of neurobiological studies, the aim of this project was to examine the influence of TG status on cortical thickness and cognitive function in a sample of schizophrenia and healthy individuals both seropositive and negative for the parasite. Methods: Schizophrenia (SCZ) = 77 (5 TG positive) and healthy control volunteers (CON) = 36 (11 TG positive) with clinical, cognitive, imaging, and available blood samples were used for the study. At least a 1-cc aliquot of serum from each subject was used for micro-enzyme-linked immunosorbent assay (ELISA) using a commercially available research kit for quantitative immunoenzymatic determination of anti-TG immunoglogulin G (IgG)-class antibodies. Cognitive and clinical functioning was assessed using a standardized battery. Structural T1-weighted images were processed using the FreeSurfer toolkit. Analyses included analysis of variance models examining differences in cortical thickness and cognition between TG seropositive (+) and negative (−) groups per condition (SCZ and CON); and Pearson correlation models of anti-TG IgG antibody titer values with thickness and behavioral variables within each condition group. Results: No significant differences in cortical thickness or cognition were observed in SCZ(+) vs SCZ(−), as well as CON(+) vs CON(−) groups, with the exception of visuospatial reasoning in CON. When correlating against anti-TG IgG titer values and cognition, significant negative relationships were noted with visuospatial reasoning (r = −.39, P = .02) and verbal memory (r = −.36, P = .03) in CON but none in SCZ. Titer values were significantly correlated with cortical thickness of the superior parietal region in SCZ (RH: r = −.24, P = .03) and at a trend level in CON (LH: r = −.31, P = .06; RH: r = −.30, P = .07). Conclusion: To our knowledge, this is the first study to examine cortical thickness in relation to cognitive function in a sample of SCZ and CON subjects with both seropositive and negative TG status. Results revealed the presence of TG appeared to primarily disrupt posterior association cortex and related functions (e.g., visuospatial reasoning) most prominently in healthy individuals but to a minor extent in schizophrenia patients. Overall, our findings suggest TG appears to exert greater influence over the neurobiology of nonpsychiatric individuals relative to psychosis, although addition research is warranted. Small seropositive sample sizes likely underpowered our ability to detect other effects.

N-Methyl-d-aspartate Modulation of Nucleus Accumbens Dopamine Release by Metabotropic Glutamate Receptors: Fast Cyclic Voltammetry Studies in Rat Brain Slices in Vitro.

The N-methyl-d-aspartate (NMDA) receptor antagonist, phencyclidine, induces behavioral changes in rodents mimicking symptoms of schizophrenia, possibly mediated through dysregulation of glutamatergic control of mesolimbic dopamine release. We tested the hypothesis that NMDA receptor activation modulates accumbens dopamine release, and that phencyclidine pretreatment altered this modulation. NMDA caused a receptor-specific, dose-dependent decrease in electrically stimulated dopamine release in nucleus accumbens brain slices. This decrease was unaffected by picrotoxin, making it unlikely to be mediated through GABAergic neurones, but was decreased by the metabotropic glutamate receptor antagonist, (RS)-α-methyl-4-sulfonophenylglycine, indicating that NMDA activates mechanisms controlled by these receptors to decrease stimulated dopamine release. The effect of NMDA was unchanged by in vivo pretreatment with phencyclidine (twice daily for 5 days), with a washout period of at least 7 days before experimentation, which supports the hypothesis that there is no enduring direct effect of PCP at NMDA receptors after this pretreatment procedure. We propose that NMDA depression of accumbal dopamine release is mediated by metabotropic glutamate receptors located pre- or perisynaptically, and suggest that NMDA evoked increased extrasynaptic spillover of glutamate is sufficient to activate these receptors that, in turn, inhibit dopamine release. Furthermore, we suggest that enduring functional changes brought about by subchronic phencyclidine pretreatment, modeling deficits in schizophrenia, are downstream effects consequent on chronic blockade of NMDA receptors, rather than direct effects on NMDA receptors themselves.

Nitric oxide in the prelimbic medial prefrontal cortex is involved in the anxiogenic-like effect induced by acute restraint stress in rats

Neurons containing the neuronal nitric oxide synthase (nNOS) enzyme are located in brain areas related to defensive behavior, such as the ventromedial prefrontal cortex (vMPFC). Rats exposed to a live predator (a cat) present anxiety-like behavior and an increased number of nNOS-positive neurons in this brain area one-week later. Moreover, stress-related behavioral changes in rodents can be prevented by systemic or local vMPFC nNOS inhibition. In the present study we investigated if acute restraint stress (RS)-induced delayed (one-week) anxiogenic-like effect was associated with increased nNOS expression or activity in the vMPFC. Furthermore, we also tested if local pharmacological nNOS inhibition would prevent stress-induced behavioral changes. Male Wistar rats were submitted to RS for 3h and tested in the elevated plus maze (EPM) 24h or 7days later. Two hours after the EPM test, their brains were removed, processed and nNOS expression in the vMPFC was evaluated by immunohistochemistry. Another group of animals was used for measuring NO metabolites (NOx; an indirect measure of NOS activity) immediately after the EPM test, 24h after RS. Independent groups had guide cannula implanted bilaterally into the prelimbic (PL) portion of vMPFC. Five to six days after surgery, the animals were submitted to RS and 24h later received local administration of the nNOS inhibitor, N-propyl-l-arginine (NPLA; 0.04nmol). They were tested in the EPM 10min later. RS-induced anxiogenic-like effect was accompanied by increased nNOS expression in the PL (p<0.05), but not in the infralimbic (IL) vMPFC, both 24h and 7days after RS. Moreover, open-arm exploration of the EPM was negatively correlated with nNOS expression (p<0.05) and NOx levels (p<0.05) in the PL. The anxiogenic-like effect observed 24h after RS was prevented by NPLA (p<0.05). Our results suggest that RS-induced anxiogenic-like effect might depend on increased nNOS-mediated signaling in the PL MPFC.