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Molecular mechanism of empathy

Final Report Summary - MOLEMPATHY (Molecular mechanism of empathy)

Empathy plays a crucial social role, allowing the sharing of experiences, needs, and goals across individuals. Anxiety, posttraumatic stress disorder, autism spectrum disorders, Asperger’s syndrome and some cerebral damage are often characterized by an inability to empathize with others. Multiple behavioral studies claim that empathy is not restricted to humans, and even rodents have been shown to demonstrate empathy-like behavior, however molecular mechanism of social behavior is still poorly understood. The present study was aimed to investigate the signal transduction pathways in brain involved in empathy. We have used an animal model based in mice acutely treated with empathogens-entactogens, pharmacological agents that produce loss of social inhibitions and closeness in humans and induce analogous prosocial and anti-aggressive effects in laboratory animals. Our experiments revealed that even single administration of N-Methyl-3,4-methylenedioxyamphetamine [MDMA, “Ecstasy”] at low dose 3 mg/kg has binary effect on behavior of mice: in some animals MDMA promotes sociability without hyperlocomotion, whereas in other mice it elevates locomotor activity without affecting sociability. Both WAY-100635, a selective antagonist of 5-HT1A receptor, and L-368899, a selective oxytocin receptor antagonist, are capable to abolish prosocial effects of MDMA. Differential quantitative analysis of brain proteome by iTRAQ technology revealed 21 proteins, highly correlating with sociability, and allowed to distinguish between entactogenic and hyperlocomotive effects of MDMA on proteome level. Multiple alterations in pathways involved in energy maintenance (Glycolysis, Sugar metabolism; Oxidative phosphorylation, Dopaminergic signaling) have been detected. Another important pathway found to be related to sociability, is gamma-aminobutyric acid [GABA] signaling. Other overrepresented pathways include GPCR signaling, synaptic vesicle cycle, WNT signaling and regulation of protein turnover (transcription, translation, modification of proteins and their proteasomal degradation). Several important post-synaptic proteins are found to be differentially expressed. In general, identified sets of differentially expressed proteins for three analyzed brain regions (cerebral cortex, hippocampus and amygdala) are quite distinct, what represents the differences in their functions, and allows hypothesizing that there are several region-specific neuronal mechanisms of prosocial behavior. Functional association network for differentially expressed proteins in cerebral cortex, hippocampus and amygdala were identified. These data may help to discover new pharmacological and genetical tools for the modulation of social behavior, but in contrast to existing entactogens, will be suitable for long-term treatment of patients suffering from social fear and low sociability.