Social Isolation: How Can the Effects on the Cholinergic System Be Isolated?

Abstract

Social species form organizations that support individuals because the consequent social behaviors help these organisms survive. The isolation of these individuals may be a stressor. We reviewed the potential mechanisms of the effects of social isolation on cholinergic signaling and vice versa how changes in cholinergic signaling affect changes due to social isolation.There are two important problems regarding this topic. First, isolation schemes differ in their duration (1–165 days) and initiation (immediately after birth to adulthood). Second, there is an important problem that is generally not considered when studying the role of the cholinergic system in neurobehavioral correlates: muscarinic and nicotinic receptor subtypes do not differ sufficiently in their affinity for orthosteric site agonists and antagonists. Some potential cholinesterase inhibitors also affect other targets, such as receptors or other neurotransmitter systems. Therefore, the role of the cholinergic system in social isolation should be carefully considered, and multiple receptor systems may be involved in the central nervous system response, although some subtypes are involved in specific functions. To determine the role of a specific receptor subtype, the presence of a specific subtype in the central nervous system should be determined using search in knockout studies with the careful application of specific agonists/antagonists.

Multitargeting nature of muscarinic orthosteric agonists and antagonists

“…Although the numbers are different, it is evident that the most abundant subtype in the striatum is M 4 mAChRs and that a substantial number of M 1 mAChRs are present. Recently, we proposed an algorithm for subtype determination ( Myslivecek, 2021 ). Here, we would like to provide the reader with a more detailed procedure for subtype identification.…”