Activation of trace amine‐associated receptor 1 (TAAR1) transiently reduces alcohol drinking in socially housed mice

Frycz, Bartosz Adam; Nowicka, Klaudia; Konopka, Anna; Hoener, Marius C.; Bulska, Ewa; Kaczmarek, Leszek; Stefaniuk, Marzena

doi:10.1111/adb.13285

Cited by 4 publications

(4 citation statements)

References 69 publications

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“…Six studies were done in the context of simple screening for potential cognitive problems in mouse models without making specific functional predictions and showed no or rather subtle Berry et al, 2012;Albuquerque et al, 2013;Too et al, 2016a;Fischer et al, 2020;Oizumi et al, 2020;Barranco et al, 2022;Li et al, 2023b Alcohol abuse disorder Radwanska and Kaczmarek, 2012;Parkitna et al, 2013;Smutek et al, 2014;Holgate et al, 2017;Mijakowska et al, 2017;Stefaniuk et al, 2017;Beroun et al, 2018;Koskela et al, 2018Koskela et al, , 2021aIman et al, 2021b;Stefaniuk et al, 2021;Hühne et al, 2022;Pagano et al, 2022;Caly et al, 2023;Frycz et al, 2023;Nalberczak-Skóra et al, 2023;Stefaniuk et al, 2023Anxiety Safi et al, 2006Jensen et al, 2016;Sano et al, 2016;Fischer et al, 2017;Raab et al, 2018;Sasaki et al, 2023 Brain lesional or ischemic damage Voikar et al, 2010;Vannoni et al, 2014;Voikar et al, 2018;Dzirkale et al, 2023 Chemical exposure Onishchenko et al, 2007;Zhu et al, 2010;Endo et al, 2012;Ogi et al, 2013Ogi et al, , 2015Aung et al, 2016;…”

Section: Analyzing Spontaneous Activity -A Simple But Effective Toolmentioning

confidence: 99%

IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system

Lipp,

Krackow,

Turkes

et al. 2024

Front. Behav. Neurosci.

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IntelliCage for mice is a rodent home-cage equipped with four corner structures harboring symmetrical double panels for operant conditioning at each of the two sides, either by reward (access to water) or by aversion (non-painful stimuli: air-puffs, LED lights). Corner visits, nose-pokes and actual licks at bottle-nipples are recorded individually using subcutaneously implanted transponders for RFID identification of up to 16 adult mice housed in the same home-cage. This allows for recording individual in-cage activity of mice and applying reward/punishment operant conditioning schemes in corners using workflows designed on a versatile graphic user interface. IntelliCage development had four roots: (i) dissatisfaction with standard approaches for analyzing mouse behavior, including standardization and reproducibility issues, (ii) response to handling and housing animal welfare issues, (iii) the increasing number of mouse models had produced a high work burden on classic manual behavioral phenotyping of single mice. and (iv), studies of transponder-chipped mice in outdoor settings revealed clear genetic behavioral differences in mouse models corresponding to those observed by classic testing in the laboratory. The latter observations were important for the development of home-cage testing in social groups, because they contradicted the traditional belief that animals must be tested under social isolation to prevent disturbance by other group members. The use of IntelliCages reduced indeed the amount of classic testing remarkably, while its flexibility was proved in a wide range of applications worldwide including transcontinental parallel testing. Essentially, two lines of testing emerged: sophisticated analysis of spontaneous behavior in the IntelliCage for screening of new genetic models, and hypothesis testing in many fields of behavioral neuroscience. Upcoming developments of the IntelliCage aim at improved stimulus presentation in the learning corners and videotracking of social interactions within the IntelliCage. Its main advantages are (i) that mice live in social context and are not stressfully handled for experiments, (ii) that studies are not restricted in time and can run in absence of humans, (iii) that it increases reproducibility of behavioral phenotyping worldwide, and (iv) that the industrial standardization of the cage permits retrospective data analysis with new statistical tools even after many years.

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Section: Analyzing Spontaneous Activity -A Simple But Effective Toolmentioning

confidence: 99%

IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system

Lipp,

Krackow,

Turkes

et al. 2024

Front. Behav. Neurosci.

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“…In this scenario, targeting TAAR1 could lead to novel approaches for the treatment of several disorders [18][19][20] including not only schizophrenia but also depression, attention deficit hyperactivity disorder, addiction [21], and metabolic diseases by means of agonist compounds, and Parkinson's disease by antagonists [22][23][24][25][26][27].…”

Section: Introductionmentioning

confidence: 99%

“…To pursue more selective TAAR1 or α 2 -ADR ligands, structural simplification of the main S18616 1 tricyclic ring has been afforded, leading to different series of more selective TAAR1 ligands [36,37] such as oxazoline derivatives (2-37) [38]. As shown in Figure 1B, these compounds can be mainly divided into benzyl-based ones (2)(3)(4), phenyl (hetero)alkyl-containing compounds (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21), and phenyl-based derivatives (22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37).…”

Section: Introductionmentioning

confidence: 99%

Discovery of a Novel Chemo-Type for TAAR1 Agonism via Molecular Modeling

Grossi,

Scarano,

Musumeci

et al. 2024

Molecules

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The search for novel effective TAAR1 ligands continues to draw great attention due to the wide range of pharmacological applications related to TAAR1 targeting. Herein, molecular docking studies of known TAAR1 ligands, characterized by an oxazoline core, have been performed in order to identify novel promising chemo-types for the discovery of more active TAAR1 agonists. In particular, the oxazoline-based compound S18616 has been taken as a reference compound for the computational study, leading to the development of quite flat and conformationally locked ligands. The choice of a “Y-shape” conformation was suggested for the design of TAAR1 ligands, interacting with the protein cavity delimited by ASP103 and aromatic residues such as PHE186, PHE195, PHE268, and PHE267. The obtained results allowed us to preliminary in silico screen an in-house series of pyrimidinone-benzimidazoles (1a–10a) as a novel scaffold to target TAAR1. Combined ligand-based (LBCM) and structure based (SBCM) computational methods suggested the biological evaluation of compounds 1a–10a, leading to the identification of derivatives 1a–3a (hTAAR1 EC50 = 526.3–657.4 nM) as promising novel TAAR1 agonists.

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“…In the brain, TAAR1 proved to be an important modulator of the major monoamine (dopamine and serotonin) and glutamate signaling pathways, directing the attention of researchers on the therapeutic implications of TAAR1 ligands in neuropsychiatric disorders [3,12,13]. The pharmaceutical company Hoffmann-La Roche was an early leader in TAAR1 drug discovery and registered several patents [14] as well as published preclinical studies [15][16][17][18][19] with selective TAAR1 agonists. TAAR1 agonists now give promise to be a new generation of antipsychotic medications, as evidenced by two compounds that have entered clinical trials, SEP-363856 (ulotaront-Sunovion) and RO6889450 (ralmitaront-La Roche) [13,20,21].…”

Section: Introductionmentioning

confidence: 99%

Discovery of Guanfacine as a Novel TAAR1 Agonist: A Combination Strategy through Molecular Modeling Studies and Biological Assays

Cichero,

Francesconi,

Casini

et al. 2023

Pharmaceuticals

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Trace amine-associated receptor 1 (TAAR1) is an attractive target for the design of innovative drugs to be applied in diverse pharmacological settings. Due to a non-negligible structural similarity with endogenous ligands, most of the agonists developed so far resulted in being affected by a low selectivity for TAAR1 with respect to other monoaminergic G protein-coupled receptors, like the adrenoreceptors. This study utilized comparative molecular docking studies and quantitative–structure activity relationship (QSAR) analyses to unveil key structural differences between TAAR1 and alpha2-adrenoreceptor (α2-ADR), with the aim to design novel TAAR1 agonists characterized by a higher selectivity profile and reduced off-target effects. While the presence of hydrophobic motives is encouraged towards both the two receptors, the introduction of polar/positively charged groups and the ligand conformation deeply affect the TAAR1 or α2-ADR putative selectivity. These computational methods allowed the identification of the α2A-ADR agonist guanfacine as an attractive TAAR1-targeting lead compound, demonstrating nanomolar activity in vitro. In vivo exploration of the efficacy of guanfacine showed that it is able to decrease the locomotor activity of dopamine transporter knockout (DAT-KO) rats. Therefore, guanfacine can be considered as an interesting template molecule worthy of structural optimization. The dual activity of guanfacine on both α2-ADR and TAAR1 signaling and the related crosstalk between the two pathways will deserve more in-depth investigation.

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Activation of trace amine‐associated receptor 1 (TAAR1) transiently reduces alcohol drinking in socially housed mice

Cited by 4 publications

References 69 publications

IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system

IntelliCage: the development and perspectives of a mouse- and user-friendly automated behavioral test system

Discovery of a Novel Chemo-Type for TAAR1 Agonism via Molecular Modeling

Discovery of Guanfacine as a Novel TAAR1 Agonist: A Combination Strategy through Molecular Modeling Studies and Biological Assays

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