Correction: Prevalence and associated risk factors for mental health problems among patients with polycystic ovary syndrome in Bangladesh: A nationwide cross-sectional study.

[This corrects the article DOI: 10.1371/journal.pone.0270102.].

Impact of Artificial Intelligence (AI) Technology in Healthcare Sector: A Critical Evaluation of Both Sides of the Coin.

The influence of artificial intelligence (AI) has drastically risen in recent years, especially in the field of medicine. Its influence has spread so greatly that it is determined to become a pillar in the future medical world. A comprehensive literature search related to AI in healthcare was performed in the PubMed database and retrieved the relevant information from suitable ones. AI excels in aspects such as rapid adaptation, high diagnostic accuracy, and data management that can help improve workforce productivity. With this potential in sight, the FDA has continuously approved more machine learning (ML) software to be used by medical workers and scientists. However, there are few controversies such as increased chances of data breaches, concern for clinical implementation, and potential healthcare dilemmas. In this article, the positive and negative aspects of AI implementation in healthcare are discussed, as well as recommended some potential solutions to the potential issues at hand.

Association between flaunting behaviors on social media and among the general population in Bangladesh: A cross-sectional study.

Background and Aims: The number of social media users is growing with each passing day at full tilt, keeping pace with digitalization and technological advances. Despite several advantages, there are also certain negative aspects to using social networking sites (SNS) for communication, amusement, self-expression, impression management, and other purposes. This study sought to investigate the association between mental health status and flaunting behaviors in social media among the general population in Bangladesh. Methods: We conducted this nationwide cross-sectional online survey among 465 people aged between 18 and 60 between October 15, 2021 and January 15, 2022. Following electronic consent, we collected the socio-demographic profiles and psychometric parameters of the respondents. Additionally, we assessed the diverse perspectives on SNS usage and its relationship to the self-reported symptoms of depression and loneliness. Results: The estimated prevalence of loneliness and depressive symptoms were 65.16% (mild: 39.57%, moderate: 16.56%, severe: 9.03%) and 55.49% (mild: 26.67%, moderate: 22.15%, severe: 6.67%), respectively. Key factors associated with flaunting on social media were mental health issues such as depression and loneliness. Several social factors were also considered, such as being young, of the male sex, unmarried, illiterate, a student, urban dwelling, average economic status, nuclear family structure, types of SNSs, checking social media first in the morning, and the use of SNS for gaining popularity. Conclusion: A significant portion of SNS users reported symptoms of mental illness. Current study findings urge for longitudinal studies with larger sample sizes to have a nearly equal distribution of users from each social media platform for in-depth exploration of how user attitudes about SNSs and site usage patterns impact the general public's mental health. We suggest that regulating SNS usage patterns and treatment approaches would improve the situation.

Combination of epigallocatechin 3 gallate and curcumin improves D-galactose and normal-aging associated memory impairment in mice.

Previously, we observed curcumin improves aging-associated memory impairment in D-galactose (D-gal) and normal-aged (NA) mice. Evidence showed that multiple agents can be used in managing aging-induced memory dysfunction, drawn by the contribution of several pathways. Curcumin and Epigallocatechin 3 gallate (EGCG) combination substantially reduced the oxidative stress that commonly mediates aging. This study examined the combined effect of EGCG and curcumin on memory improvement in two recognized models, D-gal and normal-aged (NA) mice. The co-administration of EGCG and curcumin significantly (p < 0.05) increased retention time detected by passive avoidance (PA) and freezing response determined in contextual fear conditioning (CFC) compared to the discrete administration of EGCG or curcumin. Biochemical studies revealed that the combination of EGCG and curcumin remarkably ameliorated the levels (p < 0.05) of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation compared to the monotherapy of EGCG or curcumin in mice hippocampi. The behavioral and biochemical studies revealed that the combination of EGCG and curcumin showed better improvement in rescuing aging-associated memory disorders in mice. EGCG and curcumin combination could serve as a better choice in managing aging-related memory disorders.

Assessment of vaccine perception and vaccination intention of Mpox infection among the adult males in Bangladesh: A cross-sectional study findings.

BACKGROUND: Mpox (monkeypox) infection has become a global concern for healthcare authorities after spreading in multiple non-endemic countries. Following the sudden multi-country outbreak of Mpox, the World Health Organization (WHO) declared a public health emergency of international concern. We do not have any vaccines approved for the prevention of Mpox infection. Therefore, international healthcare authorities endorsed smallpox vaccines for the prevention of Mpox disease. Here we intended to perform this cross-sectional study among the adult males in Bangladesh to assess the Mpox vaccine perception and vaccination intention. METHODS: We conducted this web-based survey among the adult males in Bangladesh from September 1, 2022, to November 30, 2022, using Google Forms. We assessed the Mpox vaccine perception and vaccination intention. We performed a chi-square test to compare vaccine perception and vaccination intention levels. Also, we performed multiple logistic regression analyses to determine the association between the study parameters and the sociodemographic profile of the participants. RESULTS: According to the present study, the Mpox vaccine perception was high among 60.54% of the respondents. Also, 60.05% of respondents showed medium vaccination intention. Mpox vaccine perception and vaccination intention were strongly associated with the sociodemographic profiles of the participants. Furthermore, we discovered a significant association between the level of education and vaccination intention among the respondents. Also, age and marital status played a role in the Mpox vaccine perception and vaccination intention. CONCLUSION: Our findings showed a significant association between sociodemographic characteristics and the Mpox vaccine perception/vaccination intention. Along with the country's long experience in mass immunization, campaigns about Covid-19 vaccines and high vaccination rates might play a role in Mpox vaccine perception and vaccination intention. We recommend more social awareness and educational communications or seminars for the target population to bring more positive changes in their attitude towards Mpox prevention.

Studies on diketopiperazine and dipeptide analogs as opioid receptor ligands.

Using the structure of gliotoxin as a starting point, we have prepared two different chemotypes with selective affinity to the kappa opioid receptor (KOR). Using medicinal chemistry approaches and structure-activity relationship (SAR) studies, structural features required for the observed affinity were identified, and advanced molecules with favorable Multiparameter Optimization (MPO) and Ligand Lipophilicity (LLE) profiles were prepared. Using the Thermal Place Preference Test (TPPT), we have shown that compound2 blocks the antinociceptive effect of U50488, a known KOR agonist. Multiple reports suggest that modulation of KOR signaling is a promising therapeutic strategy in treating neuropathic pain (NP). As a proof-of-concept study, we tested compound 2 in a rat model of NP and recorded its ability to modulate sensory and emotional pain-related behaviors. Observed in vitro and in vivo results suggest that these ligands can be used to develop compounds with potential application as pain therapeutics.

Coenzyme Q10 ameliorates carbofuran induced hepatotoxicity and nephrotoxicity in wister rats.

Carbofuran is a widely used poisonous pesticide around the world that helps to control insects during farming. Upon oral ingestion to humans, it exaggerates oxidative stress in various organs like the liver, brain, kidney, and heart. Several studies reported that oxidative stress in the liver initiates and propagates hepatic cell necrosis, ultimately resulting in hepatotoxicity. It also reported that coenzyme Q10 (CoQ10) can neutralize oxidative stress due to its antioxidant properties. However, the hepatoprotective and nephroprotective role of CoQ10 against carbofuran toxicity has not been investigated. Therefore, the present study aimed to evaluate the hepatoprotective and nephroprotective role of CoQ10 in carbofuran-induced hepatotoxicity and nephrotoxicity in a mouse model for the first time. We determined the blood serum diagnostic markers, oxidative stress parameters, antioxidant system, and histopathological characteristics of liver and kidney tissues. The administration of 100 mg/kg of CoQ10 in carbofuran-treated rats significantly attenuated AST, ALT, ALP, serum creatinine, and BUN levels. Moreover, CoQ10 (100 mg/kg) remarkably altered the level of NO, MDA, AOPP, GSH, SOD, and CAT in both the liver and kidney. The histopathological data also unveiled that CoQ10 treatment prevented inflammatory cell infiltration in carbofuran-exposed rats. Therefore, our findings infer that CoQ10 may effectively protect liver and kidney tissues against carbofuran-induced oxidative hepatotoxicity and nephrotoxicity.

Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders.

Introduction: Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. Methods: We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.2:1.0 to identify rare CNVs. To identify candidate genes within the rare CNVs, gene constraint metrics [i.e., "Critical-Exon Genes (CEGs)"] were applied to the population data. Autism Diagnostic Observation Schedule-Second Edition (ADOS-2) was followed in a subset of 95 NDD patients to assess the severity of autism and all statistical tests were performed using the R package. Results: Of all the samples assayed, 12.26% (26/212) and 57.08% (121/212) patients carried pathogenic and variant of uncertain significance (VOUS) CNVs, respectively. While 2.83% (6/212) patients' pathogenic CNVs were found to be located in the subtelomeric regions. Further burden test identified females are significant carriers of pathogenic CNVs compared to males (OR = 4.2; p = 0.0007). We have observed an increased number of Loss of heterozygosity (LOH) within cases with 23.85% (26/109) consanguineous parents. Our analyses on imprinting genes show, 36 LOH variants disrupting 69 unique imprinted genes and classified these variants as VOUS. ADOS-2 subset shows severe social communication deficit (p = 0.014) and overall ASD symptoms severity (p = 0.026) among the patients carrying duplication CNV compared to the CNV negative group. Candidate gene analysis identified 153 unique CEGs in pathogenic CNVs and 31 in VOUS. Of the unique genes, 18 genes were found to be in smaller (<1 MB) focal CNVs in our NDD cohort and we identified PSMC3 gene as a strong candidate gene for Autism Spectrum Disorder (ASD). Moreover, we hypothesized that KMT2B gene duplication might be associated with intellectual disability. Conclusion: Our results show the utility of CMA for precise genetic diagnosis and its integration into the diagnosis, therapy and management of NDD patients.

Problematic internet use and depressive symptoms among the school-going adolescents in Bangladesh during the COVID-19 pandemic: A cross-sectional study findings.

Background and Aims: Problematic internet use (PIU) by children and adolescents is a concern for many parents. Several factors, including students' education level, the method of instruction, the dependence on the internet, and their intended use of the internet, could all be contributing factors to PIU and depression. Disturbed mental health may be attributed to the cancellation of physical education classes because of the COVID-19 outbreak. This study aimed to assess the association of COVID-19 pandemic with PIU and depressive symptoms in adolescent students. Methods: We performed this cross-sectional study among 491 school-going adolescents of 10 to 16 years. Self-administered questionnaires were applied to collect sociodemographic information and the internet usage pattern of the participants. We measured the prevalence of PIU and depressive symptoms using the PIU questionnaire (PIUQ-SF-6) and patient health questionnaire-9 (PHQ-9). Results: The estimations of the risk group for PIU and depressive symptoms among school-going adolescents were 80.04% and 77.80%, respectively. The latent profiling of PIU scores for obsession, neglect, and control sub-groups were 5.82, 6.12, and 6.35, respectively. Moreover, we observed mild, moderate, and severe depressive symptoms in 48.68%, 27.70%, and 1.43% of cases. Age, education level, medium of education, financial impression, internet connection, the device used, the purpose for internet use, and the living status of respondents were significantly associated with the PIU. Reported mental health issues was associated with education level, medium of education, financial impression, and internet connection. Conclusion: The present study revealed an association of PIU and depressive symptoms with sociodemographic factors and internet usage patterns. Therefore, these results might have practical implications in clinical psychology, psychiatry, and psychotherapy. The healthcare professional can develop a context-specific comprehensive clinical intervention plan for children and adolescents.

Repositioning potentials of smallpox vaccines and antiviral agents in monkeypox outbreak: A rapid review on comparative benefits and risks.

Background and aims: There is a sought for vaccines and antiviral agents as countermeasures for the recent monkeypox outbreak. Here, we aimed to review and discuss the repurposing potentials of smallpox vaccines and drugs in monkeypox outbreaks based on their comparative benefits and risks. Therefore, we conducted this rapid review and discussed the repurposing potentials of smallpox vaccines and drugs in monkeypox infection. Methods: Here, we searched Google Scholar and PubMed for relevant information and data. We found many articles that have suggested the use of smallpox vaccines and antiviral drugs in monkeypox outbreaks according to the study findings. We read the relevant articles to extract information. Results: According to the available documents, we found two replication-competent and one replication-deficient vaccinia vaccines were effective against Orthopoxvirus. However, the healthcare authorities have authorized second-generation live vaccina virus vaccines against Orthopoxvirus in many countries. Smallpox vaccine is almost 85% effective in preventing monkeypox infection as monkeypox virus, variola virus, and vaccinia virus are similar. The United States and Canada have approved a replication-deficient third-generation smallpox vaccine for the prevention of monkeypox infection. However, the widely used second-generation smallpox vaccines contain a live virus and replicate it into the human cell. Therefore, there is a chance to cause virus-induced complications among the vaccinated subjects. In those circumstances, the available Orthopoxvirus inhibitors might be a good choice for treating monkeypox infections as they showed similar efficacy in monkeypox infection in different animal model clinical trials. Also, the combined use of antiviral drugs and vaccinia immune globulin can enhance significant effectiveness in immunocompromised subjects. Conclusion: Repurposing of these smallpox vaccines and antiviral agents might be weapons to fight monkeypox infection. Also, we recommend further investigations of smallpox vaccines and Orthopoxvirus inhibitors in a human model study to explore their exact role in human monkeypox infections.

Hematological Abnormalities and Comorbidities Are Associated With the Severity of Kidney Disease: A Hospital-Based Cross-Sectional Study in Bangladesh.

Background: Abnormalities in hematology and comorbidities might have a role in chronic kidney disease (CKD) patients. However, the exact relationships between hematological parameters and the severity of CKD are not well understood. Also, the underlying mechanisms remain under investigation. The present study aimed to evaluate the association of different blood parameters and comorbidities among hospitalized CKD patients in Bangladesh. Methods: The present study enrolled admitted CKD patients at Evercare Hospital Ltd, Dhaka, Bangladesh, from January 1, 2021, to August 1, 2021. For this study, the demographic and clinical information of the patients were collected. Then some routine blood tests for the hematological profile of CKD patients were performed. Finally, several statistical methods were performed and data interpretations were done to evaluate the role of hematological changes on CKD patients. Results: Among 300 patients, early-stage CKD patients (ESCKDP) and advanced-stage CKD patients (ASCKDP) were 153 and 147, respectively. The decreased levels of hemoglobin (Hb) and red blood cell (RBC) in ASCKDP were observed. However, the present study found increased levels of corpuscular Hb in ASCKDP than ESCKDP. Also, the present study noticed correlations between these changes and the severity of CKD. Also, we observed a significant difference in age and body mass index between ESCKDP and ASCKDP. Conclusions: Based on our results, lower Hb and RBC levels may use in assessing the severity and the treatment decisions of CKD patients in the hospital setting. Therefore, our findings may assist with developing a treatment protocol for hospitalized CKD patients.

Prevalence and associated risk factors for mental health problems among patients with polycystic ovary syndrome in Bangladesh: A nationwide cross-Sectional study.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common female reproductive endocrine problem worldwide. The prevalence of mental disorder is increasing among PCOS patients due to various physical, psychological, and social issues. Here we aimed to evaluate the mental health and associated factors among women suffering from PCOS in Bangladesh. METHODS: We performed an online cross-sectional survey among 409 participants with PCOS using Google Forms. We used structured questionnaires to collect socio-demographic information and lifestyle-related factors. Also, we applied patient health questionnaire (PHQ-9), generalized anxiety disorder (GAD-7) scale, and UCLA loneliness (UCLA-3) scale for psychometric assessment of the participants. Finally, we applied several statistical tools and performed data interpretations to evaluate the prevalence of mental health disorders and associated factors among patients with PCOS in Bangladesh. RESULTS: Prevalence of loneliness, generalized anxiety disorder and depressive illness among the women with PCOS were 71%, 88%, and 60%, respectively. Among the mental illness, mild, moderate, and severe cases were 39%, 18%, and 14% for loneliness; 39%, 23% and 26% for generalized anxiety disorder; and 35%, 18%, and 7% for depressive disorder. According to the present findings, obesity, financial condition, physical exercise, mealtime, food habit, daily water consumption, birth control method, and long-term oral contraceptive pills contribute to developing mental health disorders among females with PCOS in Bangladesh. CONCLUSION: According to present study results, high proportion of women suffering from PCOS experience several mental disorders in Bangladesh. Although several socio-demographic and lifestyle-related factors were found to be associated with the poor mental health of women with PCOS; however, PCOS itself is a condition that favors poor physical and psychological health. Therefore, we recommend proper treatment, public awareness, and a healthy lifestyle to promote the good mental health of women suffering from PCOS.

Curcumin improves D-galactose and normal-aging associated memory impairment in mice: In vivo and in silico-based studies.

Aging-induced memory impairment is closely associated with oxidative stress. D-Galactose (D-gal) evokes severe oxidative stress and mimics normal aging in animals. Curcumin, a natural flavonoid, has potent antioxidant and anti-aging properties. There are several proteins like glutathione S-transferase A1 (GSTA1), glutathione S-transferase omega-1 (GSTO1), kelch-like ECH-associated protein 1 (KEAP1), beta-secretase 1 (BACE1), and amine oxidase [flavin-containing] A (MAOA) are commonly involved in oxidative stress and aging. This study aimed to investigate the interaction of curcumin to these proteins and their subsequent effect on aging-associated memory impairment in two robust animal models: D-Gal and normal aged (NA) mice. The aging mice model was developed by administering D-gal intraperitoneally (i.p). Mice (n = 64) were divided into the eight groups (8 mice in each group): Vehicle, Curcumin-Control, D-gal (100mg/kg; i.p), Curcumin + D-gal, Astaxanthin (Ast) + D-gal, Normal Aged (NA), Curcumin (30mg/kg Orally) + NA, Ast (20mg/kg Orally) + NA. Retention and freezing memories were assessed by passive avoidance (PA) and contextual fear conditioning (CFC). Molecular docking was performed to predict curcumin binding with potential molecular targets. Curcumin significantly increased retention time (p < 0.05) and freezing response (p < 0.05) in PA and CFC, respectively. Curcumin profoundly ameliorated the levels of glutathione, superoxide dismutase, catalase, advanced oxidation protein products, nitric oxide, and lipid peroxidation in mice hippocampi. In silico studies revealed favorable binding energies of curcumin with GSTA1, GSTO1, KEAP1, BACE1, and MAOA. Curcumin improves retention and freezing memory in D-gal and nature-induced aging mice. Curcumin ameliorates the levels of oxidative stress biomarkers in mice. Anti-aging effects of curcumin could be attributed to, at least partially, the upregulation of antioxidant enzymes through binding with GSTA1, GSTO1, KEAP1, and inhibition of oxidative damage through binding with BACE1 and MAOA.

Pharmaceutical quality evaluation of marketed vildagliptin tablets in Bangladesh based on the United States Pharmacopeia specifications.

Continuous monitoring of pharmaceutical products is vital because it matters to human health. Here we aimed to assess the quality parameters of commercially available vildagliptin tablets in Bangladesh. We tested the tablets for the content uniformity, hardness, friability, disintegration, dissolution, and potency. Then, we fitted the dissolution data with kinetic models to investigate the release pattern of the studied brands. Moreover, we applied a mathematical model-independent approach to compare the dissolution profiles of the brands. The interchangeability was determined using difference and similarity factors. Weight variation, friability, and hardness were between 150.35±1.26 to 230.8±1.98 mg, 0 to 0.88%, and 47.3±5.09 to 108.1±1.92 N, respectively. All tablets disintegrated within 0.54±2.85 to 7.69±2.14 min in distilled water. The potency of tablets in 0.1 N HCl and PBS (pH 6.8) were between 97.67±2.58 to 105±0.95% and 99±4.63 to 105±1.65%, respectively. The drug release (%) in 0.1 N HCl and phosphate-buffered saline (PBS) (pH 6.8) after 60 min were between 99.37±1.80 to 111.09±0.64% and 96.59±3.52 to 109.57±0.53%, respectively. All the brands complied with the United States Pharmacopeia (USP) specification for physicochemical properties. Also, we observed the drug release patterns of vildagliptin tablets matched with different kinetic models. We found only one substitutable brand with the standard product regardless of the dissolution medium. In-vitro chemical equivalence is not always consistent with bioequivalence. Therefore, continuous evaluation of marketed products is essential to ensure the desired quality.

Hematological abnormalities and comorbidities are associated with COVID-19 severity among hospitalized patients: Experience from Bangladesh.

BACKGROUND: The hematological abnormalities are assumed to be involved in the disease progression of COVID-19. However, the actual associations between specific blood parameters and COVID-19 are not well understood. Here we aimed to assess the correlations between hematological parameters and the severity of COVID-19. METHODS: We included COVID-19 patients who were admitted to Evercare Hospital Ltd, Dhaka, Bangladesh, between November 10, 2020, to April 12, 2021, with a confirmed case of RT-PCR test. We recorded demographic information, clinical data, and routine hematological examination results of all COVID-19 patients. We performed statistical analyses and interpretation of data to compare severe COVID-19 patients (SCP) and non-severe COVID-19 patients (NSCP). RESULTS: The age and BMI of the admitted COVID-19 patients were 48.79±8.53 years and 25.82±3.75 kg/m2. This study included a total of 306 hospitalized COVID-19 patients. Among them, NSCP and SCP were 198 and 108, respectively. And we recorded 12 deaths from SCP. We observed the alterations of several hematological parameters between SCP and NSCP. Among them, we noticed the increased levels of C-reactive protein (CRP), d-dimer, and ferritin showed good indicative value to evaluate the severity of COVID-19. Also, there were positive correlations among these parameters. Moreover, we found correlations between the outcomes of COVID-19 patients with patient's demographics and comorbid diseases. CONCLUSION: Based on our results, CRP, d-dimer, and ferritin levels at admission to hospitals represent simple assessment factors for COVID-19 severity and the treatment decisions at the hospital setup. These blood parameters could serve as indicators for the prognosis and severity of COVID-19. Therefore, our study findings might help to develop a treatment protocol for COVID-19 patients at the hospital setup.

Therapeutic Potentials of Colocasia affinis Leaf Extract for the Alleviation of Streptozotocin-Induced Diabetes and Diabetic Complications: In vivo and in silico-Based Studies.

INTRODUCTION: Hypoglycemia in diabetes mellitus (DM) correlates with hepatic impairment, nephropathy, lipid abnormalities, and oxidative stress and subsequently complicates the disease pathogenesis. Medicinal plants have been used for the management of diabetes since ancient times. In this study, we explored the potentials of Colocasia affinis (CA), a plant known to possess anti-allergic and anti-inflammatory activities, as a remedy for diabetes and related complications. METHODS: We induced diabetes in rats using a single intraperitoneal dose (65 mg/kg) of streptozotocin (STZ). We next treated the rats with an ethanolic extract of leaves of CA to reveal its antidiabetic and organ-protective potentials. Biomarkers of diabetes, inflammation, and oxidative stress were measured using biochemical and histopathological analysis. We also performed molecular docking for three major phytochemicals (kaempferol, myricetin, and rosmarinic acid) of CA. RESULTS: Oral administration of the CA leaves extract at 250 mg/kg and 500 mg/kg doses decreased blood glucose level significantly (p<0.05) in STZ-induced diabetic rats. The extract also considerably attenuated plasma HbA1c levels and normalized blood lipids, glycogen, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Additionally, treatment with the extract improved kidney complications by decreasing serum creatinine and blood urea nitrogen (BUN) levels. Furthermore, CA leaves extract normalized nitric oxide (NO) and advance oxidative protein products (AOPP) in diabetic rats. The extract also showed significant improvement of the antioxidant enzymes glutathione dismutase (GSH) and superoxide dismutase (SOD) at a dose of 500 mg/kg. Besides, histological investigation demonstrated attenuation of inflammation of the vital organs, including the liver and the kidney. In silico studies revealed that three major phytochemicals (kaempferol, myricetin, and rosmarinic acid) of the ethanolic extract of leaves of CA can inhibit several molecular targets of diabetes and inflammation. CONCLUSION: Collectively, our results demonstrated the therapeutic potentials of CA for the mitigation of diabetes and diabetic complications.

Blockade of the M1 muscarinic acetylcholine receptors impairs eyeblink serial feature-positive discrimination learning in mice.

The serial feature-positive discrimination task requires the subjects to respond differentially to the identical stimulus depending on the temporal context given by a preceding cue stimulus. In the present study, we examined the involvement of the M1 muscarinic acetylcholine receptors using a selective M1 antagonist VU0255035 in the serial feature-positive discrimination task of eyeblink conditioning in mice. In this task, mice received a 2-s light stimulus as the conditional cue 5 or 6 s before the presentation of a 350-ms tone conditioned stimulus (CS) paired with a 100-ms peri-orbital electrical shock (cued trials), while they did not receive the cue before the presentation of the CS alone (non-cued trials). Each day mice randomly received 30 cued and 30 non-cued trials. We found that VU0255035 impaired acquisition of the conditional discrimination as well as the overall acquisition of the conditioned response (CR) and diminished the difference in onset latency of the CR between the cued and non-cued trials. VU0255035 administration to the control mice after sufficient learning did not impair the pre-acquired conditional discrimination or the CR expression itself. These effects of VU0255035 were almost similar to those with the scopolamine in our previous study, suggesting that among the several types of muscarinic acetylcholine receptors, the M1 receptors may play an important role in the acquisition of the conditional discrimination memory but not in mediating the discrimination itself after the memory had formed in the eyeblink serial feature-positive discrimination learning.