Putative Trace-Amine Associated Receptor 5 (TAAR5) Agonist α-NETA Increases Electrocorticogram Gamma-Rhythm in Freely Moving Rats

Trace Amine-Associated Receptor 5 Provides Olfactory Input Into Limbic Brain Areas and Modulates Emotional Behaviors and Serotonin Transmission

“…Indeed, in our study, we observed significant alterations in various measures of anxiety and affectivity of TAAR5-KO mice in a number of behavioral tests used to test putative anxiolytic and antidepressant drugs. Importantly, the lack of TAAR5 results in the anxiolytic/antidepressant-like phenotype, while recently identified putative nonselective TAAR5 receptor agonist 2-(alpha-naphthoyl) ethyltrimethylammonium iodide (alpha-NETA) increases cortical gamma-rhythm in rats (Belov et al, 2019), causes deficits in sensorimotor gating in rats (Aleksandrov et al, 2018a), and increases mismatch negativity (MMN)-like responses in rats and mice (Aleksandrov et al, 2018b(Aleksandrov et al, , 2019 in a manner consistent with psychosis-related cognitive deficits described in humans and experimental animals (Light and Swerdlow, 2015).…”

“…HPLC measurements of tissue 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) were carried out as described before Belov et al (2019). Briefly, the striatum, the frontal cortex, the hypothalamus, and the hippocampus were dissected on an ice, frozen in a liquid nitrogen, and stored at −80 • C. The samples for analysis were homogenized in 0.1 M HClO 4 , centrifuged (10 min, +4 • C; 14,000× g) and filtered using centrifuge filter units [polyvinylidene fluoride (PVDF) membrane; pore size, 0.22 µm, Millipore, Burlington, MA, USA].…”

Pattern of TAAR5 Expression in the Human Brain Based on Transcriptome Datasets Analysis

“…Results of animal studies indicate that TAAR5 might be involved in the pathogenesis of neuropsychiatric diseases. TAAR5-KO mice demonstrate anxiolytic/antidepressant-like phenotype [5]; at the same time animals treated with non-selective TAAR5 agonist α-NETA have disrupted synchronization of cortical gamma rhythms [22] and deregulated sensory gating [20,43] mirroring pathological changes in schizophrenia. Several studies included in the meta-analysis were devoted to demonstrating the transcriptome dis-balances in schizophrenia, bipolar disorder or major depressive disorder, but only one demonstrated significant downregulation of TAAR5 in the prefrontal cortex in major depressive disorder.…”

“…Opposite effects were demonstrated in animals, treated with putative TAAR5 agonist α-NETA. This substance disrupts sensory information processing and alters brain electrophysiological activity in mice in a manner consistent with psychotic states [19][20][21][22]. Most importantly, prominent expression of TAAR5 was observed not only in the olfactory bulb but also in numerous limbic brain regions receiving olfactory input, such as the anterior olfactory nucleus, the olfactory tubercle, the orbitofrontal cortex, the amygdala, the hippocampus, the piriform cortex, the entorhinal cortex, the nucleus accumbens, and the thalamic and hypothalamic nuclei.…”

Neurodegenerative and metabolic disorders, mediated by the trace amines and their receptors

“…Агонист TAAR5 α-NETA опосредует передачу дофамина в стриатум, что вызывает значительные изменения гамма-ритма мозговой активности, которые могут быть важными прогностическими факторами при лечении пациентов с шизофренией и другими нейродегенеративными заболеваниями, связанными с дофаминовой системой. Эти наблюдения указывают на возможную роль TAAR5 в модуляции когнитивных функций при патологии головного мозга [49].…”