{"title":"Sex differences in exploratory behavior of rats successfully performing the object-in-place recognition memory test","authors":"","doi":"10.1016/j.bbr.2024.115303","DOIUrl":"10.1016/j.bbr.2024.115303","url":null,"abstract":"<div><div>Male and female rodents display unique search strategies when exploring new and familiar environments. Sex differences are well-documented in the literature and may be observed in tasks that rely on spontaneous exploration (e.g., recognition memory tests). Therefore, we assessed patterns of male and female rat behavior in the object-in-place (OiP) test, a common recognition memory paradigm involving object-location associations. Twelve male and 12 female adult Long Evans rats were tested four times in the 1-h OiP test and exploratory behaviors were compared during habituation, sample, and test phases. Results revealed that females moved faster and farther than males, showed increased immobility frequency and reduced immobility duration, reduced outer zone mobility duration, and increased inner zone entrances, compared to males during habituations. During sample phases, female rats moved faster than males, displayed reduced immobility frequency in the inner zone, and demonstrated consistent distance travelled across repeated sessions; conversely, male rats moved less in later sessions and exhibited increased mobility frequency in the outer zone. Analyses comparing test phase behavior revealed females continued to move faster than males; however, no other sex differences were observed. These findings are consistent with previous literature highlighting unique sex differences in explorative behaviors during recognition testing. Sex differences in locomotion and mobility state behaviors may be more indicative of individual motivation and search strategy between the sexes and less indicative of recognition memory.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A new 2-hit model combining serine racemase deletion and maternal separation displays behavioral and cognitive deficits associated with schizophrenia","authors":"","doi":"10.1016/j.bbr.2024.115301","DOIUrl":"10.1016/j.bbr.2024.115301","url":null,"abstract":"<div><div>Schizophrenia (SCZ) is a multifactorial psychotic disorder characterized by positive and negative symptoms as well as cognitive impairments. To advance the current treatments, it is important to improve animal models by considering the multifactorial etiology, thus by combining different risk factors. The objective of our study was to explore in a new mouse model, the impact of genetic deletion of <em>serine racemase</em> (genetic vulnerability) combined with an early stress factor induced by maternal separation (early environmental exposure) in the context of SCZ development. The face validity of the model was assessed through a wide range of behavioral experiments. The 2-hit mice displayed an increased locomotor activity mimicking positive symptoms, working memory impairment, cognitive deficits and recognition memory alterations, which could reflect neophobia. This new multifactorial model therefore presents an interesting phenotype for modelling animal model with partial behavioral and cognitive deficits associated with SCZ.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The dopamine transporter inhibition using GBR 12909 as a novel pharmacological tool to assess bipolar disorder-like neurobehavioral phenotypes in zebrafish","authors":"","doi":"10.1016/j.bbr.2024.115302","DOIUrl":"10.1016/j.bbr.2024.115302","url":null,"abstract":"<div><div>Dopamine (DA) is a neurotransmitter that plays an important role in brain physiology. Changes in DA-mediated signaling have been implicated with the pathophysiology of various neuropsychiatric conditions. Bipolar disorder (BD) is a mental disorder, characterized by alterning between manic/hypomanic and depressive mood. In experimental research, the pharmacological inhibition of DA reuptake using GBR 12909 serves as a tool to elicit BD-like phenotypes. Alternative model organisms, such as the zebrafish (<em>Danio rerio</em>), have been considered important systems for investigating the neurobehavioral changes involved in different neuropsychiatric conditions, including BD. Here, we discuss the use of GBR 12909 as a novel pharmacological strategy to mimic BD-like phenotypes in zebrafish models. We also emphasize the well-conserved DA-mediated signaling in zebrafish and the early expression of dopaminergic biomarkers in the brain, especially focusing on dopamine transporter (DAT), the main target of GBR 12909. Finally, we discuss potential advantages and limitations in the field, the perspectives of using GBR 12909 in BD research, and how distinct validation criteria (<em>i.e.</em>, face, predictive, and construct validity) can be assessed in translational approaches using zebrafish-based models.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Between Scylla and Charybdis: Fixed-ratio avoidance response effort and unavoidable shock extinction in humans","authors":"","doi":"10.1016/j.bbr.2024.115299","DOIUrl":"10.1016/j.bbr.2024.115299","url":null,"abstract":"<div><div>Avoidance of potential threat may become maladaptive when it is indiscriminate and resistant to change. Here, we investigated the resistance to change of high and low avoidance response effort when avoidance extinction involved unavoidable presentations of the aversive event (shock) in humans. Following fear conditioning, participants prevented upcoming shock delivery by responding on high (i.e., fixed ratio, FR-20) and low (FR-5) negative reinforcement schedules. Next, noneliminable shock was used for an avoidance extinction procedure whereby responding was followed by, rather than prevented, shock. During a subsequent standard extinction and response prevention test phase, we found that High effort (FR-20) avoidance would be more readily extinguished than Low effort (FR-5) avoidance. It was also predicted that fear, threat expectancy, and psychophysiological (skin conductance) responses would decrease on avoidable trials and increase on unavoidable trials before extinguishing to low levels. It was found that in the final extinction re-test phase when avoidance was possible, responding increased, particularly for low effort cues. Both fear and expectancy remained high. Individual differences on clinically relevant measures of trait anxiety, intolerance of uncertainty and experiential avoidance were associated with greater levels of fear and threat expectancy. Overall, unavoidable shock extinction may hold promise for further translational investigations of avoidance learning, extinction, and clinical treatment development.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142493952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Involvement of the serotonergic, GABAergic and glutamatergic systems of the rostral anterior cingulate cortex in the trait and state anxiety of adult male Wistar rats.","authors":"","doi":"10.1016/j.bbr.2024.115298","DOIUrl":"10.1016/j.bbr.2024.115298","url":null,"abstract":"<div><div>Despite significant advancements to understand of the neural circuitry involved in anxiety, the neurobiology of trait anxiety remains unclear. The rostral anterior cingulate cortex (rACC) and various pathways have been implicated in its regulation, making it a key to trait anxiety. The present study aimed to investigate the role of these neurotransmitter systems in the rACC in trait anxiety. Since trait anxiety is known to modulate state anxiety, we further investigated this relationship. Specifically, in Experiment I, we used animals with high trait anxiety; in Experiment II, we used animals with low trait anxiety; and in Experiment III, we used animals with medium trait anxiety. Before each behavioral assessment, drugs that either increased or decreased serotonergic (Fluoxetine or WAY-100635), GABAergic (Muscimol or Bicuculline), and glutamatergic (NMDA or Ketamine) neurotransmission in the rACC were administered, along with their respective controls. Additionally, in Experiment IV, all animals from the previous experiments were subjected to the Elevated Plus Maze (EPM) and Hole board (HB) test and evaluated without taking into account their trait anxiety levels. The results of the present study showed that, in Exp I, the modulation of the serotonergic, GABAergic and glutamatergic systems in the rACC decreased trait anxiety in highly anxious rats, while by submitting the animals to HB, the administration of fluoxetine increased state anxiety. In Exp II, the modulation of all systems increased trait anxiety in rats with low trait anxiety, whereas, in HB, state anxiety levels were increased with the administration of NMDA. In Exp III, only the modulation of the glutamatergic system, with NMDA, increased both trait and state anxiety levels. However, none of the evaluated neurotransmitter systems altered the state anxiety modeled in the EPM. Overall, the results of the present study provide new insights into the role of the neurotransmitter systems in the rACC in the regulation of trait anxiety and state anxiety.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Towards imagined speech: Identification of brain states from EEG signals for BCI-based communication systems","authors":"","doi":"10.1016/j.bbr.2024.115295","DOIUrl":"10.1016/j.bbr.2024.115295","url":null,"abstract":"<div><h3>Background</h3><div>The electroencephalogram (EEG) based brain-computer interface (BCI) system employing imagined speech serves as a mechanism for decoding EEG signals to facilitate control over external devices or communication with the external world at the moment the user desires. To effectively deploy such BCIs, it is imperative to accurately discern various brain states from continuous EEG signals when users initiate word imagination.</div></div><div><h3>New method</h3><div>This study involved the acquisition of EEG signals from 15 subjects engaged in four states: resting, listening, imagined speech, and actual speech, each involving a predefined set of 10 words. The EEG signals underwent preprocessing, segmentation, spatio-temporal and spectral analysis of each state, and functional connectivity analysis using the phase locking value (PLV) method. Subsequently, five features were extracted from the frequency and time-frequency domains. Classification tasks were performed using four machine learning algorithms in both pair-wise and multiclass scenarios, considering subject-dependent and subject-independent data.</div></div><div><h3>Results</h3><div>In the subject-dependent scenario, the random forest (RF) classifier achieved a maximum accuracy of 94.60 % for pairwise classification, while the artificial neural network (ANN) classifier achieved a maximum accuracy of 66.92 % for multiclass classification. In the subject-independent scenario, the random forest (RF) classifier achieved maximum accuracies of 81.02 % for pairwise classification and 55.58 % for multiclass classification. Moreover, EEG signals were classified based on frequency bands and brain lobes, revealing that the theta (<em>θ</em>) and delta (<em>δ</em>) bands, as well as the frontal and temporal lobes, are sufficient for distinguishing between brain states.</div></div><div><h3>Conclusion</h3><div>The findings promise to develop a system capable of automatically segmenting imagined speech segments from continuous EEG signals.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"An unescapable looming threat paradigm for assessing anxiety-like responses in rats","authors":"","doi":"10.1016/j.bbr.2024.115296","DOIUrl":"10.1016/j.bbr.2024.115296","url":null,"abstract":"<div><div>Rapidly approaching visual stimuli (i.e. looming objects) are known to evoke unconditioned defense responses across species. In rodents, this threat reactivity repertoire includes freezing and fleeing behavior. Although components of the circuitry underlying unconditioned response to a looming threat have been elucidated, both a temporal characterization and drug effects on the freezing response have not yet been reported. Here, we describe a modified version of a looming threat task in which no escape route is available. In this task, we observed unconditioned freezing prior to, during, and after exposure to a looming threat stimulus. In Long Evans (LE) and Sprague-Dawley (SD) rats, we report looming stimulus-specific freezing response. We further explored the specificity and pharmacosensitivity of this response in male and female LE rats. Administration of a GABA-A receptor negative allosteric modulator (FG-7142) did not re-establish freezing in habituated animals; however, administration of a GABA-A receptor positive allosteric modulator (diazepam) in naïve LEs significantly reduced freezing during the post-looming period in a sex-dependent manner. Presentation of an unescapable looming stimulus results in freezing that extends beyond the acute threat exposure. Because freezing responses outlast the initial threat, and display only modest sensitivity to conventional anxiolytic therapy, this may represent a platform for screening agents in treatment-refractory anxiety.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"HINT1 promotes neuronal apoptosis and triggers schizophrenia-like behavior in rats","authors":"","doi":"10.1016/j.bbr.2024.115297","DOIUrl":"10.1016/j.bbr.2024.115297","url":null,"abstract":"<div><div>This study aims to investigate the mechanism by which Histidine triad nucleotide-binding protein 1 (HINT1) promotes hippocampal neuronal apoptosis, triggering schizophrenia (SZ<strong>)-</strong>like behavior in rats. By establishing a rat SZ-like model, we assessed learning, memory, emotional response, and cognitive function through the Morris Water Maze, auditory startle response, and open field tests. HINT1 expression in the hippocampus was analyzed via RT-PCR and Western blot. We also created a HINT1 overexpression model in hippocampal neuronal cells to analyze its effects on cell proliferation and apoptosis. This analysis was conducted using the CCK-8 assay and flow cytometry, along with the quantification of apoptosis-related proteins and neurotrophic factors. Our findings indicated that the SZ-like model rats exhibited diminished learning and memory abilities, altered emotional reactions, and impaired cognitive functions, alongside a notable increase in HINT1 mRNA and protein levels. HINT1 overexpression was observed to inhibit hippocampal neuronal cell proliferation and promote apoptosis, with an increase in the expression of pro-apoptotic proteins and a decrease in neurotrophic factors. These results suggest HINT1's role in the onset and development of SZ-like behavior through its upregulation and induction of apoptosis in hippocampal neuronal cells, underlining its potential as a therapeutic target.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effect of chronic alcohol exposure and single-prolonged stress on conditioned fear behavior","authors":"","doi":"10.1016/j.bbr.2024.115294","DOIUrl":"10.1016/j.bbr.2024.115294","url":null,"abstract":"<div><div>The present study investigated the impact of chronic intermittent ethanol (CIE) exposure and single-prolonged stress (SPS) on the acquisition of fear memories in both male and female Wistar rats. Adult rats were first subjected to CIE by vapor inhalation followed by SPS. Following a subsequent 8-day incubation period, the rats underwent a Pavlovian fear conditioning procedure (tone-shock pairings) followed by cued-tone extinction training, and then testing of extinction recall memory and fear renewal memory. In control animals that had not been exposed to either CIE or SPS, female rats exhibited significantly lower levels of freezing compared to male rats during tone-shock pairings. This lower level of freezing in female rats during conditioning was associated with an increased speed of movement compared to males. Also compared to males, female rats exhibited lower levels of fear extinction, recall, and renewal. Exposure to CIE, SPS, or CIE+SPS had no effect on freezing during the cued-conditioning, extinction, or extinction recall phases of the testing procedure in either sex. In fear renewal, CIE exposure decreased freezing in male but not female rats, while SPS increased freezing in female but not male rats. CIE exposure significantly reduced freezing during the fear renewal phase. Taken together, these results provide further evidence that male and female rats adopt different avoidance strategies for threat responding. These results also revealed that prior exposure to CIE, SPS, or CIE+SPS had minimal effects on threat responding using conditioned freezing as an indicator of fear responsivity.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142446292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"DNA methylation profiles of transgenerational rat hyperactivity primed by silver nanoparticles: Comparison with valproate model rats of autism","authors":"","doi":"10.1016/j.bbr.2024.115293","DOIUrl":"10.1016/j.bbr.2024.115293","url":null,"abstract":"<div><div>There is an increasing body of evidence suggesting that a single exposure to certain chemicals can have transgenerational effects, with the underlying mechanism believed to be epigenetic. However, it remains largely unknown whether psychiatric conditions like ADHD or autism, induced by environmental chemicals, can be inherited across generations. Pregnant rats were purchased from a commercial breeder. On the 7th day of gestation (E7), they were divided into two groups: one group was orally exposed to silver nanoparticles (AgNP; 4 mg/kg), while the control group received vehicle alone. The subsequent generation (F1) underwent spontaneous motor activity (SMA) measurements at 8–11 weeks of age. For breeding at 26 weeks of age, rats with higher SMA were selected from hyperactive litters, while untreated rats were randomly selected. This process was continued for four generations in both groups. The AgNP-primed rats at 4th generation displayed significantly higher SMA, 1.8 times greater than that of untreated rats. Intraperitoneal injection of valproic acid (150 mg/kg), an epigenetic modifier to 5-day-old rats causes adult hyperactivity (1.4-fold), suggesting that epigenetic modification contributes to rat hyperactivity. Global DNA methylation profiles in the mesencephalon were positively correlated in both groups of hyperactive rats. Furthermore, there were 7–8 common genes showing both hypermethylation and hypomethylation, which are involved in neuronal development, neuronal function, transcriptional activity, DNA binding activity, cell differentiation, ubiquitination processes, or histone modification, including Pax 6 and Mecp 2. Thus, it is most likely that rats retain hyperactivity through mesencephalic DNA methylation status across transgeneration.</div></div>","PeriodicalId":8823,"journal":{"name":"Behavioural Brain Research","volume":null,"pages":null},"PeriodicalIF":2.6,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"心理学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}