Enhanced Aggression, Reduced Self-Grooming Behavior and Altered 5-HT Regulation in the Frontal Cortex in Mice Lacking Trace Amine-Associated Receptor 1 (TAAR1).

The Trace Amine-Associated Receptor 1 (TAAR1) is one of the six functional receptors belonging to the family of monoamine-related G protein-coupled receptors (TAAR1-TAAR9) found in humans. However, the exact biological mechanisms of TAAR1 central and peripheral action remain to be fully understood. TAAR1 is widely expressed in the prefrontal cortex and several limbic regions, interplaying with the dopamine system to modulate the reward circuitry. Recent clinical trials suggest the efficacy of TAAR1 agonists as potential novel antipsychotic agents. Here, we characterize behavioral and neurochemical phenotypes of TAAR1 knockout mice, focusing on aggression and self-grooming behavior that both strongly depend on the monoaminergic signaling and cortico-striatal and cortico-limbic circuits. Overall, we report increased aggression in these knockout mice in the resident-intruder test, accompanied by reduced self-grooming behavior in the novelty-induced grooming test, and by higher cortical serotonin (5-HT) tissue levels. Further studies are necessary to explore whether TAAR1-based therapies can become potential novel treatments for a wide range of neuropsychiatric disorders associated with aggression.

Expression of the growth hormone secretagogue receptor 1a (GHS-R1a) in the brain.

The review presents data on the expression of growth hormone secretagogue receptor 1a (GHS-R1a) in the brain regions in model animals (zebrafish, rodents, primates), and in the human brain. Studies show widespread distribution of the receptor in the brain, which evidences the involvement of the receptor in many physiological processes. Using various organisms, data have been obtained regarding the participation of the GHS-R1a in the regulation of the anti- and pro-inflammatory response, proliferation, and apoptosis. It is known that the receptor plays an important role in eating behavior and is also involved in the pathogenetic mechanisms of drug addiction, obesity, and chronic alcohol consumption. Based on this, research is underway with the use of various therapeutic agents that can be used for the pharmacological correction of these conditions. This review also presents hypothetical pathways of intracellular signaling, in which GHS-R1a may participate. A complete understanding of these mechanisms has not yet been reached. The ghrelin intracellular signaling seem to be specific to brain region and, probably, also depend on the metabolic or stress status of the organism.