ABSTRACT
Trace amines have been reported to be neuromodulators of monoaminergic systems. Trace amines receptor 5 (TAAR5) is expressed in several regions of mice central nervous system, such as amygdala, arcuate nucleus and ventromedial hypothalamus, but very limited information is available on its functional role. The purpose of this study is to examine the effect of TAAR5 agonist alpha-NETA on the generation of mismatch negativity (MMN) analogue in C57BL/6 mice. Event-related potentials have been recorded from awake mice in oddball paradigms before and after the alpha-NETA administration. Alpha-NETA has been found to decrease N40 MMN-like difference, which resulted from the increased response to standard stimuli. An opposite effect has been found for the P80 component: the amplitude increased in response both to standard and deviant stimuli. A significant increase in N40 peak latency after the alpha-NETA administration has been found. This may suggest a reduced speed of information processing similar to the increase in P50 and N100 components latencies in schizophrenia patients. These results provide new evidence for a role of TAAR5 in cognitive processes.
Subject(s)
Acoustic Stimulation/methods , Evoked Potentials, Auditory/physiology , Quaternary Ammonium Compounds/pharmacology , Receptors, G-Protein-Coupled/agonists , Receptors, G-Protein-Coupled/physiology , Wakefulness/physiology , Animals , Electroencephalography/methods , Evoked Potentials, Auditory/drug effects , Male , Mice , Mice, Inbred C57BL , Quaternary Ammonium Compounds/chemistry , Wakefulness/drug effectsABSTRACT
The potential contribution of trace amines (TA) to the pathophysiology of neuropsychiatric disorders makes it interesting to examine the effect of TA receptor ligands on schizophrenia biomarkers. We studied the effect of systemic administration of a putative Trace Amine-Associated Receptor 5 (TAAR5) agonist, alpha-NETA (2-(alpha-naphthoyl) ethyltrimethylammonium iodide), on the amplitude of the N40 event related potentials component and on the sensory gating (SG) index in C57BL/6 mice. It was found that low doses of alpha-NETA (2.5â¯mg/kg and 5â¯mg/kg) do not elicit a significant effect on the parameters of the N40 component and the SG index. However, the higher dose of alpha-NETA (10â¯mg/kg) induces a significant effect on the N40 component, but since a decrease in amplitude is observed on both the first and second stimuli in the pair, the SG index does not change. Thus, alpha-NETA administration causes a steady decrease in the N40 amplitude in response to both the first and second stimuli in the paired-click paradigm, and an increase in the N40 peak latency.
Subject(s)
Auditory Cortex/drug effects , Evoked Potentials, Auditory/drug effects , Naphthalenes/pharmacology , Quaternary Ammonium Compounds/pharmacology , Sensory Gating/drug effects , Acoustic Stimulation , Animals , Electroencephalography , Male , Mice , Mice, Inbred C57BLABSTRACT
Trace amines are structurally close to classical monoamines and dysregulation in trace amines and/or their receptors might contribute to pathology of mental disorders. The study was aimed to investigate the effect of recently identified Trace Amine-Associated Receptor 5 (TAAR5) agonist 2-(alpha-naphthoyl)ethyltrimethylammonium iodide (alpha-NETA) on sensory gating (SG) in awake freely moving rats. SG was studied in paired-click paradigm and SG index was calculated as difference in event related potentials component N40 amplitudes to the first and second stimulus in the pair. The 1â¯mg/kg dose of alpha-NETA as well as the control injection of saline had no significant effects on the SG index. However, higher doses of alpha-NETA (3 and 5â¯mg/kg) significantly decreased the SG index. The change in the SG index was mainly due to a decrease in the N40 amplitude, and the 5â¯mg/kg dose caused the N40 decrease both in response to the first and second stimulus in the pair. Thus, TAAR5 activation can influence SG, indicating the potential role of trace amines and TAAR5 in sensory information dosing.