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  1. Article ; Online: The dopamine D1 receptor positive allosteric modulator, DETQ, improves cognition and social interaction in aged mice and enhances cortical and hippocampal acetylcholine efflux.

    Rajagopal, Lakshmi / Huang, Mei / Mahjour, Sanaz / Ryan, Chelsea / Elzokaky, Ahmad / Svensson, Kjell A / Meltzer, H Y

    Behavioural brain research

    2023  Volume 459, Page(s) 114766

    Abstract: Dopamine (DA) D1 and D2 receptors (Rs) are critical for cognitive functioning. D1 positive allosteric modulators (D1PAMs) activate D1Rs without desensitization or an inverted U-shaped dose response curve. DETQ, [2-(2,6-dichlorophenyl)-1-((1S,3R)-3-( ... ...

    Abstract Dopamine (DA) D1 and D2 receptors (Rs) are critical for cognitive functioning. D1 positive allosteric modulators (D1PAMs) activate D1Rs without desensitization or an inverted U-shaped dose response curve. DETQ, [2-(2,6-dichlorophenyl)-1-((1S,3R)-3-(hydroxymethyl)-5-(2-hydroxypropan-2-yl)-1-methyl-3,4-dihydroisoquinolin-2(1H)-yl)ethan-1-one] is highly selective for the human D1Rs as shown in humanized D1R knock-in (hD1Ki) mice. Here, we have ascertained the efficacy of DETQ in aged [13-23-month-old (mo)] hD1Ki mice and their corresponding age-matched wild-type (WT; C57BL/6NTac) controls. We found that in aged mice, DETQ, given acutely, subchronically, and chronically, rescued both novel object recognition memory and social behaviors, using novel object recognition (NOR) and social interaction (SI) tasks, respectively without any adverse effect on body weight or mortality. We have also shown, using in vivo microdialysis, a significant decrease in basal DA and norepinephrine, increase in glutamate (Glu) and gamma-amino butyric acid (GABA) efflux with no significant changes in acetylcholine (ACh) levels in aged vs young mice. In young and aged hD1Ki mice, DETQ, acutely and subchronically increased ACh in the medial prefrontal cortex and hippocampal regions in aged hD1Ki mice without affecting Glu. These results suggest that the D1PAM mechanism is of interest as potential treatment for cognitive and social behavioral deficits in neuropsychiatric disorders including but not restricted to neurodegenerative disorders, such as Parkinson's disease.
    MeSH term(s) Mice ; Humans ; Animals ; Aged ; Infant ; Acetylcholine ; Social Interaction ; Mice, Inbred C57BL ; Dopamine ; Glutamic Acid ; Hippocampus/metabolism ; Receptors, Dopamine D1/metabolism ; Cognition
    Chemical Substances Acetylcholine (N9YNS0M02X) ; Dopamine (VTD58H1Z2X) ; Glutamic Acid (3KX376GY7L) ; Receptors, Dopamine D1
    Language English
    Publishing date 2023-12-03
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2023.114766
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Pimavanserin augments the efficacy of atypical antipsychotic drugs in a mouse model of treatment-refractory negative symptoms of schizophrenia.

    Rajagopal, L / Ryan, C / Elzokaky, A / Burstein, E S / Meltzer, H Y

    Behavioural brain research

    2021  Volume 422, Page(s) 113710

    Abstract: Negative symptoms are a core, pervasive, and often treatment-refractory phenotype of schizophrenia, one which contributes to poor functional outcome, ability to work, pursue educational goals, and quality of life, as well as caretaker burden. Improvement ...

    Abstract Negative symptoms are a core, pervasive, and often treatment-refractory phenotype of schizophrenia, one which contributes to poor functional outcome, ability to work, pursue educational goals, and quality of life, as well as caretaker burden. Improvement of negative symptoms in some patients with schizophrenia has been reported with some atypical antipsychotic drugs [AAPDs], but improvement is absent in many patients and partial in others. Therefore, more effective treatments are needed, and better preclinical models of negative symptoms are needed to identify them. Sub-chronic [sc] treatment of rodents with phencyclidine [PCP], a noncompetitive N-methyl-d-aspartate [NMDAR] antagonist, produces deficits in social interactions [SI] that have been widely studied as a model of negative symptoms in schizophrenia. Acute restraint stress [ARS] also provides a model of treatment-refractory negative symptoms [TRS] to AAPDs. By themselves, in sc-PCP mice, the AAPDs, risperidone, olanzapine, and aripiprazole, but not the selective 5-HT
    MeSH term(s) Animals ; Antipsychotic Agents/administration & dosage ; Antipsychotic Agents/pharmacology ; Disease Models, Animal ; Drug Synergism ; Drug Therapy, Combination ; Male ; Mice ; Mice, Inbred C57BL ; Piperidines/administration & dosage ; Piperidines/pharmacology ; Schizophrenia, Treatment-Resistant/drug therapy ; Urea/administration & dosage ; Urea/analogs & derivatives ; Urea/pharmacology
    Chemical Substances Antipsychotic Agents ; Piperidines ; Urea (8W8T17847W) ; pimavanserin (JZ963P0DIK)
    Language English
    Publishing date 2021-12-11
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2021.113710
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Anti-Vaccine Attitudes among Adults in the U.S. during the COVID-19 Pandemic after Vaccine Rollout.

    Choi, Jasmin / Lieff, Sarah A / Meltzer, Gabriella Y / Grivel, Margaux M / Chang, Virginia W / Yang, Lawrence H / Des Jarlais, Don C

    Vaccines

    2022  Volume 10, Issue 6

    Abstract: Even though vaccination is the most effective measure against COVID-19 infections, vaccine rollout efforts have been hampered by growing anti-vaccine attitudes. Based on current knowledge, we identified three domains (beliefs, discrimination, and news) ... ...

    Abstract Even though vaccination is the most effective measure against COVID-19 infections, vaccine rollout efforts have been hampered by growing anti-vaccine attitudes. Based on current knowledge, we identified three domains (beliefs, discrimination, and news) as our correlates of primary interest to examine the association with anti-vaccine attitudes. This is one of the first studies to examine key correlates of anti-vaccine attitudes during the critical early stages of vaccine implementation in the United States. An online survey was administered in May 2021 to a non-representative, nationally based sample of adults (N = 789). Using multivariable logistic regression analysis, we found that individuals who expressed worry about COVID-19 (OR = 0.34, 95% CI 0.21, 0.55) and had greater knowledge of COVID-19 (OR = 0.50, 95% CI 0.25, 0.99) were less likely to hold anti-vaccine attitudes. Conversely, individuals who held stigmatizing views of COVID-19 (OR = 2.47, 95% CI 1.53, 3.99), had experienced racial discrimination (OR = 2.14, 95% CI 1.25, 3.67) and discrimination related to COVID-19 (OR = 2.84, 95% CI 1.54, 5.24), and who had been watching Fox News (OR = 3.95, 95% CI 2.61, 5.97) were more likely to hold anti-vaccine attitudes. These findings suggest COVID-19 beliefs, experiences of discrimination, and news sources should be considered when designing targeted approaches to address the anti-vaccine movement.
    Language English
    Publishing date 2022-06-10
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2703319-3
    ISSN 2076-393X
    ISSN 2076-393X
    DOI 10.3390/vaccines10060933
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Neurosteroid pregnenolone sulfate, alone, and as augmentation of lurasidone or tandospirone, rescues phencyclidine-induced deficits in cognitive function and social interaction.

    Rajagopal, L / Soni, D / Meltzer, H Y

    Behavioural brain research

    2018  Volume 350, Page(s) 31–43

    Abstract: Background: Pregnenolone sulfate (PregS), an endogenous neurosteroid, which negatively and positively modulates gamma amino butyric acid subunit A (GABA: Methods: We tested whether PregS, by itself, and in combination with Lur or Tan could rescue ... ...

    Abstract Background: Pregnenolone sulfate (PregS), an endogenous neurosteroid, which negatively and positively modulates gamma amino butyric acid subunit A (GABA
    Methods: We tested whether PregS, by itself, and in combination with Lur or Tan could rescue persistent deficits produced by subchronic treatment with the NMDAR antagonist, phencyclidine (PCP)-in episodic memory, executive functioning, and social behavior, using novel object recognition (NOR), operant reversal learning (ORL), and social interaction (SI) tasks, in male C57BL/6 J mice.
    Results: PregS (10, but not 3 mg/kg) significantly rescued subchronic PCP-induced NOR and SI deficits. Co-administration of sub-effective doses (SEDs) of PregS (3 mg/kg) + Lur (0.1 mg/kg) or Tan (0.03 mg/kg) rescued scPCP-induced NOR and SI deficits. Further, PregS (30, but not 10 mg/kg) rescued PCP-induced ORL deficit, as did the combination of SED PregS (10 mg/kg) +SED Lur (1 mg/kg) or Tan (1 mg/kg).
    Conclusion: PregS was effective alone and as adjunctive treatment for treating two types of cognitive impairments and negative symptoms in this schizophrenia model. Further study of the mechanisms by which PregS alone and in combination with AAPDs and 5-HT
    MeSH term(s) Animals ; Antipsychotic Agents/pharmacology ; Cognition/drug effects ; Drug Therapy, Combination ; Interpersonal Relations ; Isoindoles/pharmacology ; Lurasidone Hydrochloride/pharmacology ; Male ; Mice, Inbred C57BL ; Neurotransmitter Agents/pharmacology ; Phencyclidine ; Piperazines/pharmacology ; Pregnenolone/pharmacology ; Pyrimidines/pharmacology ; Random Allocation ; Receptors, GABA-A/metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Schizophrenia/drug therapy ; Schizophrenia/metabolism ; Schizophrenic Psychology
    Chemical Substances Antipsychotic Agents ; Isoindoles ; Neurotransmitter Agents ; Piperazines ; Pyrimidines ; Receptors, GABA-A ; Receptors, N-Methyl-D-Aspartate ; pregnenolone sulfate (04Y4D91RG0) ; tandospirone (190230I669) ; Pregnenolone (73R90F7MQ8) ; Phencyclidine (J1DOI7UV76) ; Lurasidone Hydrochloride (O0P4I5851I)
    Language English
    Publishing date 2018-05-24
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2018.05.005
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Respiratory Microbial Co-infection With SARS-CoV-2

    Massey, B. W. / Jayathilake, K. / Meltzer, H. Y.

    Frontiers in Microbiology

    Abstract: Co-infection with additional pathogens is a well-known feature of pandemics We determined the prevalence and type of a wide variety of respiratory pathogens in 12,075 United States subjects tested for SARS-CoV-2 infection in March and April 2020 ... ...

    Abstract Co-infection with additional pathogens is a well-known feature of pandemics We determined the prevalence and type of a wide variety of respiratory pathogens in 12,075 United States subjects tested for SARS-CoV-2 infection in March and April 2020 Infections with other respiratory pathogens, which on their own produce at least some SARS-CoV-2 symptoms including mortality, were present in both SARS-CoV-2 + and SARS-CoV-2- subjects Non-SARS-CoV-2 infection rates were significantly higher in SARS-CoV-2 + (86%) patients than SARS-CoV-2– patients (76%) (p < 0 0001) Among the co-pathogens present in both subject groups were K pneumoniae and M catarrhalis which can produce serious respiratory illness on their own, Advanced age and nursing home status were associated with higher SARS-CoV-2 + and co-infection rates Testing for the presence of co-pathogens going forward will assist in the diagnosis and optimal treatment of suspected SARS-CoV-2 respiratory infections in the current pandemic
    Keywords covid19
    Publisher WHO
    Document type Article
    Note WHO #Covidence: #776214
    Database COVID19

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  6. Article: Single-cell analysis of the nervous system at small and large scales with instant partitions.

    Frazel, P W / Fricano-Kugler, K / May-Zhang, A A / O'Dea, M R / Prakash, P / Desmet, N M / Lee, H / Meltzer, R H / Fontanez, K M / Hettige, P / Agam, Y / Lithwick-Yanai, G / Lipson, D / Luikart, B W / Dasen, J D / Liddelow, S A

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Single-cell RNA sequencing is a new frontier across all biology, particularly in neuroscience. While powerful for answering numerous neuroscience questions, limitations in sample input size, and initial capital outlay can exclude some researchers from ... ...

    Abstract Single-cell RNA sequencing is a new frontier across all biology, particularly in neuroscience. While powerful for answering numerous neuroscience questions, limitations in sample input size, and initial capital outlay can exclude some researchers from its application. Here, we tested a recently introduced method for scRNAseq across diverse scales and neuroscience experiments. We benchmarked against a major current scRNAseq technology and found that PIPseq performed similarly, in line with earlier benchmarking data. Across dozens of samples, PIPseq recovered many brain cell types at small and large scales (1,000-100,000 cells/sample) and was able to detect differentially expressed genes in an inflammation paradigm. Similarly, PIPseq could detect expected and new differentially expressed genes in a brain single cell suspension from a knockout mouse model; it could also detect rare, virally-la-belled cells following lentiviral targeting and gene knockdown. Finally, we used PIPseq to investigate gene expression in a nontraditional model species, the little skate (Leucoraja erinacea). In total, PIPSeq was able to detect single-cell gene expression changes across models and species, with an added benefit of large scale capture and sequencing of each sample.
    Language English
    Publishing date 2023-07-18
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.07.14.549051
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article: Association of Serotonin

    Li, Jiang / Hashimoto, Hitoshi / Meltzer, Herbert Y

    Frontiers in psychiatry

    2019  Volume 10, Page(s) 58

    Abstract: There is conflicting evidence for the association between genetic polymorphisms in the serotonin (5-HT) ...

    Abstract There is conflicting evidence for the association between genetic polymorphisms in the serotonin (5-HT)
    Language English
    Publishing date 2019-02-15
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2564218-2
    ISSN 1664-0640
    ISSN 1664-0640
    DOI 10.3389/fpsyt.2019.00058
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Behavioral Correlates of COVID-19 Worry: Stigma, Knowledge, and News Source.

    Meltzer, Gabriella Y / Chang, Virginia W / Lieff, Sarah A / Grivel, Margaux M / Yang, Lawrence H / Des Jarlais, Don C

    International journal of environmental research and public health

    2021  Volume 18, Issue 21

    Abstract: Non-adherence to COVID-19 guidelines may be attributable to low levels of worry. This study assessed whether endorsing COVID-19-stigmatizing restrictions, COVID-19 knowledge, and preferred news source were associated with being 'very worried' versus 'not ...

    Abstract Non-adherence to COVID-19 guidelines may be attributable to low levels of worry. This study assessed whether endorsing COVID-19-stigmatizing restrictions, COVID-19 knowledge, and preferred news source were associated with being 'very worried' versus 'not at all' or 'somewhat' worried about contracting COVID-19. Survey data were collected in July-August 2020 from N = 547 New York State (NYS) and N = 504 national Amazon MTurk workers. Respondents who endorsed COVID-19 stigmatizing restrictions (NYS OR 1.96; 95% CI 1.31, 2.92; national OR 1.80; 95% CI 1.06, 3.08) and consumed commercial news (NYS OR 1.89; 95% CI 1.21, 2.96; national OR 1.93; 95% CI 1.24, 3.00) were more likely to be very worried. National respondents who consumed
    MeSH term(s) Anxiety ; COVID-19 ; Cross-Sectional Studies ; Humans ; SARS-CoV-2 ; Surveys and Questionnaires
    Language English
    Publishing date 2021-10-30
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2175195-X
    ISSN 1660-4601 ; 1661-7827
    ISSN (online) 1660-4601
    ISSN 1661-7827
    DOI 10.3390/ijerph182111436
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The Adult Neck Mass: Predictors of Malignancy.

    Kshirsagar, Rijul S / Anderson, Meredith / Boeckermann, Lauren M / Gilde, Jason / Shen, Joseph Y / Meltzer, Charles / Wang, Kevin H

    Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery

    2021  Volume 165, Issue 5, Page(s) 673–681

    Abstract: Objective: Distinguishing benign from malignant adult neck masses can be challenging because data to guide risk assessment are lacking. We examined patients with neck masses from an integrated health system to identify patient and mass factors ... ...

    Abstract Objective: Distinguishing benign from malignant adult neck masses can be challenging because data to guide risk assessment are lacking. We examined patients with neck masses from an integrated health system to identify patient and mass factors associated with malignancy.
    Study design: Retrospective cohort.
    Setting: Kaiser Permanente Northern California.
    Methods: The medical records of adults referred to otolaryngology in 2017 for a neck mass were evaluated. Bivariate and multivariable logistic regression analyses were performed.
    Results: Malignancy was found in 205 (5.0%) of the cohort's 4103 patients. Patient factors associated with malignancy included sex, age, and race/ethnicity. Males had more than twice the odds of malignancy compared with females (adjusted odds ratio [aOR] = 2.38). Malignancy rates increased with age, ranging from 2.1% for patients younger than 40 years to 8.4% for patients 70 years or older. White non-Hispanic patients had 1.75 times the risk of malignancy compared with patients of other race/ethnicities. The percentage of patients with malignancy increased with increasing minimum mass dimension, from 3.0% in patients with mass size <1 cm to over 31% in patients with mass sizes 2 cm or larger (
    Conclusion: Most neck masses referred to otolaryngology were not malignant. Increasing age, male sex, white non-Hispanic ethnicity, increasing minimum mass dimension, multiple neck masses, or heterogeneous architecture/ill-defined borders were associated with malignancy.
    MeSH term(s) Adult ; Aged ; Biopsy ; Diagnosis, Differential ; Female ; Head and Neck Neoplasms/pathology ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Registries ; Retrospective Studies
    Language English
    Publishing date 2021-03-09
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 392085-9
    ISSN 1097-6817 ; 0161-6439 ; 0194-5998
    ISSN (online) 1097-6817
    ISSN 0161-6439 ; 0194-5998
    DOI 10.1177/0194599821996293
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  10. Article ; Online: Blonanserin reverses the phencyclidine (PCP)-induced impairment in novel object recognition (NOR) in rats: role of indirect 5-HT(1A) partial agonism.

    Horiguchi, M / Meltzer, H Y

    Behavioural brain research

    2013  Volume 247, Page(s) 158–164

    Abstract: Blonanserin is an atypical antipsychotic drug (APD) which, compared to other atypical APDs, is a relatively selective serotonin (5-HT)2A and dopamine D2 antagonist. Comparing blonanserin with more broadly acting atypical APDs could be useful to test the ... ...

    Abstract Blonanserin is an atypical antipsychotic drug (APD) which, compared to other atypical APDs, is a relatively selective serotonin (5-HT)2A and dopamine D2 antagonist. Comparing blonanserin with more broadly acting atypical APDs could be useful to test the contributions of actions at other monoamine receptors, e.g. 5-HT1A receptors, to the reversal of PCP-induced novel object recognition (NOR) deficit. In this study, we tested the effect of blonanserin alone, and in combination with 5-HT1A agents, on NOR deficit induced by subchronic treatment with the N-methyl-D-aspartate (NMDA) receptor antagonist, phencyclidine (PCP; 2 mg/kg), b.i.d., for 7 days. Blonanserin, 1mg/kg, but not 0.3mg/kg, improved the PCP-induced NOR deficit. However, at 1mg/kg, object exploration was diminished. Co-administration of sub-effective doses of blonanserin (0.3 mg/kg) and the 5-HT1A partial agonist, tandospirone (0.2 mg/kg), significantly reversed the NOR deficit without diminishing activity during the acquisition or retention periods. The combination of WAY100635 (0.6 mg/kg), a 5-HT1A antagonist, and blonanserin (1 mg/kg), also diminished object exploration which prevented assessment of the effect of this combination on NOR. WAY100635 (0.6 mg/kg) blocked the ameliorating effect of risperidone (0.1 mg/kg), another atypical APD with low affinity for 5-HT1A receptors, but did not impair exploration. These results suggest that blonansein and risperidone, atypical APDs which lack a direct action on 5-HT1A receptors require 5-HT1A receptor stimulation to reverse the subchronic PCP-induced NOR deficit and provide a support for clinical trial of blonanserin in combination with tandospirone to ameliorate cognitive impairment in schizophrenia and to have fewer side effects.
    MeSH term(s) Animals ; Female ; Isoindoles/pharmacology ; Phencyclidine/pharmacology ; Piperazines/pharmacology ; Piperidines/pharmacology ; Pyridines/pharmacology ; Pyrimidines/pharmacology ; Rats ; Rats, Long-Evans ; Receptor, Serotonin, 5-HT1A/metabolism ; Recognition (Psychology)/drug effects ; Serotonin 5-HT1 Receptor Agonists/pharmacology ; Serotonin 5-HT2 Receptor Antagonists/pharmacology
    Chemical Substances Isoindoles ; Piperazines ; Piperidines ; Pyridines ; Pyrimidines ; Serotonin 5-HT1 Receptor Agonists ; Serotonin 5-HT2 Receptor Antagonists ; Receptor, Serotonin, 5-HT1A (112692-38-3) ; tandospirone (190230I669) ; N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide (71IH826FEG) ; blonanserin (AQ316B4F8C) ; Phencyclidine (J1DOI7UV76)
    Language English
    Publishing date 2013-06-15
    Publishing country Netherlands
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 449927-x
    ISSN 1872-7549 ; 0166-4328
    ISSN (online) 1872-7549
    ISSN 0166-4328
    DOI 10.1016/j.bbr.2013.03.027
    Database MEDical Literature Analysis and Retrieval System OnLINE

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