Evaluation of Approach to a Conspecific and Blood Biochemical Parameters in TAAR1 Knockout Mice

Zhukov, Ilya S.; Ptukha, Maria; Zolotoverkhaya, Ekaterina A.; Sinitca, E. L.; Tissen, Ilia Yu.; Karpova, I. V.; Volnova, Anna; Gainetdinov, Raul R.

doi:10.3390/brainsci12050614

Cited by 6 publications

(8 citation statements)

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“…Notably, Lynch et al (Lynch et al 2013) found no difference in sucrose consumption between WT and Taar1 KO mice, suggesting that TAAR1 does not affect natural reward. It was also shown that deletion of Taar1 did not significantly affect sexual motivation in mice (Zhukov et al 2022). Although RO5263397 attenuated the expression of behavioral sensitization to methamphetamine, and reduced methamphetamine self-administration it did not alter cue-induced reinstatement of sucrose-seeking behavior (Jing et al 2014).…”

Section: Discussionmentioning

confidence: 99%

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

Frycz

Nowicka

Konopka

et al. 2022

Preprint

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Rationale: Trace amine-associated receptor 1 (TAAR1) is an important modulator of dopaminergic neurotransmission and has been recognized as a potential therapeutic target for alcoholism treatment. The interaction of alcohol with the dopamine reward system in the brain may promote the development of alcohol abuse. Objectives: The aim of the study was to evaluate the role of TAAR1 receptor stimulation on alcohol drinking behaviors in mice. Methods: We investigated the blood-brain barrier (BBB) penetration of the RO5256390 in mice by mass spectrometry. Then, wild-type (WT) mice were housed in an automatic behavioral system, IntelliCage, and habituated to drinking alcohol. The animals were further administrated either with RO526390 (10 mg/kg, intraperitoneally) or vehicle and studied on alcohol consumption, alcohol consumption after abstinence, and motivation to drink alcohol. Results: We found that RO5256390 highly penetrated the BBB. R05256390 administration also transiently reduced alcohol consumption and alcohol consumption after abstinence in mice with a high preference for alcohol in comparison to high-drinking mice from the vehicle group. Furthermore, RO5256390 attenuated the motivation for drinking alcohol. Conclusions: Our data suggest that activation of Taar1 reduces alcohol drinking behavior in mice.

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Section: Discussionmentioning

confidence: 99%

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

Frycz

Nowicka

Konopka

et al. 2022

Preprint

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“…Furthermore, TAAR9 knockout rats demonstrated decreased low-density lipoprotein cholesterol levels in comparison to control rats [ 54 ]. However, when biochemical and hematological parameters were analyzed in TAAR1 knockout (TAAR1-KO) mice, only the creatine kinase levels were found to be minimally changed in TAAR1-KO male mice [ 55 ]. Thus, we speculated that the high fructose diet may potentially reveal specific metabolism changes in the TAAR1-KO mice.…”

Section: Introductionmentioning

confidence: 99%

“…Among the biochemical indicators, one of the most valuable is protein metabolism, including total protein, urea, and transaminase activity (AST, ALT, and De Ritis ratio). The aspartate aminotransferase (AST) activity plays an important role in the regulation of catabolic reactions of the body, and alanine aminotransferase (ALT)–anabolic reactions, which prove that these biochemical indicators are not only the result of the cytolysis of myocardial and liver cells, respectively [ 55 , 59 ].…”

Section: Introductionmentioning

confidence: 99%

“…The level of locomotor activity is usually studied using the open field test. The anxiety level was assessed using the elevated plus maze (EPM) test, which allows for the assessment of the severity of the emotional reaction of fear and anxiety, motor activity, the speed of orienting reactions, and other behavioral changes [ 18 , 55 , 58 , 59 ]. One of the important tasks of the study was the search for new behavioral indicators to assess the depression-like behavior of TAAP1-KO mice, based on the microstructure of grooming [ 60 , 61 ].…”

Section: Introductionmentioning

confidence: 99%

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Protein Metabolism Changes and Alterations in Behavior of Trace Amine-Associated Receptor 1 Knockout Mice Fed a High-Fructose Diet

Apryatin

Zhukov

Zolotoverkhaya³

et al. 2023

Neurology International

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Trace amines and their receptors are a family of G protein-coupled receptors widely distributed in the central nervous system and periphery. The trace amine-associated receptor 1 (TAAR1) plays a significant role as a therapeutic target for schizophrenia, depression, diabetes, and obesity. In this study, TAAR1 knockout mice and WT groups were tested in conditions of a high-fructose diet. The consumption of a high-fructose diet may be due to the influence on the metabolism processes by dopamine in the brain, neuromotor function, and level of anxiety of TAAR1 knockout mice. During a comparative analysis of behavioral, biochemical, and morphological parameters, significant differences were found between liver and biochemical parameters, the regulation of protein metabolism (AST/ALT ratio, creatine kinase activity, urea), and alterations in behavior. An elevated plus maze analysis showed the influence of fructose and genetic factors on the level of anxiety. A new marker of the grooming microstructure (depression ratio) was tested, which showed high efficiency as a marker of depression-like behavioral changes and a possible association with dopamine-dependent regulation of protein metabolism. These results confirm a possible association of the TAAR1 gene knockout with an increase in catabolic reaction levels by AST/ALT-dependent and possible dopamine-mediated protein metabolism regulation and depression-like behavior.

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“…TAAR9 is also known to be expressed at a low level in immune cells, including NK-cells, T-cells, B-cells, and monocytes [ 15 ]. TAAR1 and TAAR9 elimination in knockout rodents is associated with minor deregulation of lipid and protein metabolism [ 16 ], which becomes more pronounced under a high-carbohydrate diet [ 17 ]. Interestingly, total cholesterol and low-density lipoproteins are decreased in TAAR9-KO animals.…”

Section: Introductionmentioning

confidence: 99%

Gut Microbiota Alterations in Trace Amine-Associated Receptor 9 (TAAR9) Knockout Rats

et al. 2022

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Trace amine-associated receptors (TAAR1-TAAR9) are a family of G-protein-coupled monoaminergic receptors which might have great pharmacological potential. It has now been well established that TAAR1 plays an important role in the central nervous system. Interestingly, deletion of TAAR9 in rats leads to alterations in the periphery. Previously, we found that knockout of TAAR9 in rats (TAAR9-KO rats) decreased low-density lipoprotein cholesterol levels in the blood. TAAR9 was also identified in intestinal tissues, and it is known that it responds to polyamines. To elucidate the role of TAAR9 in the intestinal epithelium, we analyzed TAAR9-co-expressed gene clusters in public data for cecum samples. As identified by gene ontology enrichment analysis, in the intestine, TAAR9 is co-expressed with genes involved in intestinal mucosa homeostasis and function, including cell organization, differentiation, and death. Additionally, TAAR9 was co-expressed with genes implicated in dopamine signaling, which may suggest a role for this receptor in the regulation of peripheral dopaminergic transmission. To further investigate how TAAR9 might be involved in colonic mucosal homeostasis, we analyzed the fecal microbiome composition in TAAR9-KO rats and their wild-type littermates. We identified a significant difference in the number of observed taxa between the microbiome of TAAR9-KO and wild-type rats. In TAAR9-KO rats, the gut microbial community became more variable compared with the wild-type rats. Furthermore, it was found that the family Saccharimonadaceae, which is one of the top 10 most abundant families in TAAR9-KO rat feces, is almost completely absent in wild-type animal fecal samples. Taken together, these data indicate a role of TAAR9 in intestinal function.

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Evaluation of Approach to a Conspecific and Blood Biochemical Parameters in TAAR1 Knockout Mice

Cited by 6 publications

References 50 publications

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

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

Protein Metabolism Changes and Alterations in Behavior of Trace Amine-Associated Receptor 1 Knockout Mice Fed a High-Fructose Diet

Gut Microbiota Alterations in Trace Amine-Associated Receptor 9 (TAAR9) Knockout Rats

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