Abstract
The appropriate display of social behavior is critical for the well-being and survival of an individual. In many psychiatric disorders, including social anxiety disorder, autism spectrum disorders, depression and schizophrenia social behavior is severely impaired. Selective targeting of metabotropic glutamate receptors (mGluRs) has emerged as a novel treatment strategy for these disorders. In this review, we describe some of the behavioral paradigms used to assess different types of social behavior, such as social interaction, social memory, aggressive behavior and sexual behavior. We then focus on the effects of pharmacological modulation of mGluR1-8 on these types of social behavior. Indeed, accumulating evidence indicates beneficial effects of selective ligands of specific mGluRs in ameliorating innate or pharmacologically-induced deficits in social interaction and social memory as well as in reducing aggression in rodents. We emphasize the importance of future studies investigating the role of selective mGluR ligands on different types of social behavior to provide a better understanding of the neural mechanisms involved which, in turn, might promote the development of selective mGluR-targeted tools for the improved treatment of psychiatric disorders associated with social deficits.
Highlights
L-glutamate represents the main excitatory neurotransmitter in the mammalian central nervous system (CNS)
Given that olfaction is critical for the appropriate display of social behavior in rodents, including social recognition and initiation of aggressive behaviors, these results indicate that mGluR7-mediated olfactory processing in the bed nucleus of the stria terminalis (BNST) is essential for inter-male aggression [130]
Several lines of evidence suggest a beneficial effect of selective ligands of specific metabotropic glutamate receptors (mGluRs) on abnormal social behavior, such as impaired social interaction, deficits in social memory or heightened aggression
Summary
L-glutamate represents the main excitatory neurotransmitter in the mammalian central nervous system (CNS). Allosteric agonists bind to the allosteric binding site and directly activate the receptor even in the absence of an orthosteric ligand. Allosteric modulators do not activate the receptor directly but indirectly influence or modulate the effects of the orthosteric ligand. Group I mGluRs can modulate additional signaling pathways and activate a wide range of downstream effectors, including phospholipase D and several protein kinase pathways, such as casein kinase 1, Jun kinase, cyclin-dependent protein kinase 5, the mammalian target of rapamycin (mTOR)/p70 S6 kinase pathway and components of the mitogen-activated protein kinase/extracellular receptor kinase (MAPK/ERK) pathway [10,11,12]. Group II and III mGluRs are coupled predominantly to Gi/o proteins, which inhibit adenylyl cyclase and directly regulate ion channels and other downstream signaling molecules via release of Gβγ subunits. We will show that the discovery of selective ligands for mGluRs created potentially novel therapeutic strategies for the treatment of psychiatric disorders associated with social deficits
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