Molecular and neurocircuitry mechanisms of social avoidance

Abstract

Humans and animals live in social relationships shaped by actions of approach and avoidance. Both are crucial for normal physical and mental development, survival, and well-being. Active withdrawal from social interaction is often induced by the perception of threat or unpleasant social experience and relies on adaptive mechanisms within neuronal networks associated with social behavior. In case of confrontation with overly strong or persistent stressors and/or dispositions of the affected individual, maladaptive processes in the neuronal circuitries and its associated transmitters and modulators lead to pathological social avoidance. This review focuses on active, fear-driven social avoidance, affected circuits within the mesocorticolimbic system and associated regions and a selection of molecular modulators that promise translational potential. A comprehensive review of human research in this field is followed by a reflection on animal studies that offer a broader and often more detailed range of analytical methodologies. Finally, we take a critical look at challenges that could be addressed in future translational research on fear-driven social avoidance.

Binge-like Alcohol Exposure in Adolescence: Behavioural, Neuroendocrine and Molecular Evidence of Abnormal Neuroplasticity… and Return

“…We employed a modification of the social interaction test, where an experimental animal can freely move towards or away from the compartment of the arena of a nonmanipulated social partner. Here, social avoidance reflects anxiety-like behaviour under social circumstances, as social approach is also directed by motivation [ 68 , 69 , 70 ]. Reduced motivational salience associated with natural rewarding stimuli is specifically reported in social anxiety disorders and substance abuse, suggesting an involvement of DA-driven reward circuitry [ 71 ].…”

“…On the striatal post-synaptic side, we observed a progressive switch in D1R- and D2R-mRNA expression, with D1R decreasing and D2R increasing during withdrawal. Although currently it is not possible to prove a direct causal relationship, the peculiar dynamics of the striatal components of the DA system may contribute to the increase in social avoidance observed at WD1; indeed, a reduced DA-ergic input corresponds to an increase in social avoidance [ 68 ]. The framework changes at WD10, when the increase in DA synthesis is associated with an increase in DA reuptake from the synaptic cleft, displaying a decrease in D1R and an increase in D2R expression.…”

Neural versus alternative integrative systems: molecular insights into origins of neurotransmitters

“…Remarkably, both the formation of social relationships and complex behavioural integrations were performed by balancing similarly diverse subsets of transmitters [37,[79][80][81][82][83][84][85][86] as in early branching animal lineages. Thus, the broadest spectrum of nearly all studied behaviours is inherently traced to multiple transmitter pathways, and the transmitter organization as well as synaptic and non-synaptic integration of behaviors are intrinsically embedded in every neural circuit from a comb jelly to Octopus.…”

Transcriptomic and Network Analyses Reveal Immune Modulation by Endocannabinoids in Approach/Avoidance Traits

“…Individual differences in A/A traits originate from differences in predisposition toward rewarding or punitive stimuli, respectively. While most studies addressed the differences in the conflict paradigms by manipulating the amygdala-frontal network [ 4 , 5 , 7 , 47 , 48 , 49 , 50 , 51 , 52 ], in the present study we faced the A/A traits investigating the molecular differences. Interestingly, the spontaneous individual differences that characterize the three sub-populations of AV, BA, and AP mice are associated with differences in CB1 density in the amygdala [ 3 , 4 , 5 ].…”