The Role of Metabotropic Glutamate Receptors in Social Behavior in Rodents

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.

Effect of Aggressive Experience in Female Syrian Hamsters on Glutamate Receptor Expression in the Nucleus Accumbens

“…Collectively, these results further provide evidence for an inverse role between mGluR1a and mGluR5 (Gross et al, 2016;Turner et al, 2018b), a reciprocal role between NR2A and NR2B in long-term potentiation and long-term depression (Massey et al, 2004;Bartlett et al, 2007), and differences in NMDAR function and learning and memory (Bar-Shira et al, 2015). In other words, these results provide support for the theory that mGluR1a and mGluR5 activation have opposite roles in NAc synaptic morphology, neuronal transmission and behavior (Dewing et al, 2007;Staffend and Meisel, 2012;Staffend et al, 2014;Been et al, 2016;Gross et al, 2016;Pitchers et al, 2016) through differences in their association with specific NMDAR subunits (Yashiro and Seki, 2017;Zoicas and Kornhuber, 2019). In agreement with previous literature, there was also a positive correlation in the expression of GluA1 and GluA2 (Diering and Huganir, 2018).…”

“…It is theorized that increases in the strength of synaptic transmission underlie the rewarding consequences of stimuli (Kasai et al, 2003;Malenka, 2003;Ebner et al, 2018;Turner et al, 2018a). Thus, this study was the first to investigate if aggression might result in increases in molecular markers of postsynaptic plasticity and excitatory synaptic transmission and increases in the strength of the associations between these postsynaptic proteins and glutamate receptors in the NAc (Pitchers et al, 2012;Bredewold et al, 2015;Garcia-Pardo et al, 2019;Zoicas and Kornhuber, 2019).…”

Chemogenetic manipulation of the bed nucleus of the stria terminalis counteracts social behavioral deficits induced by early life stress in C57BL/6J mice

“…One possibility is that ELS may induce heightened basal or stimuli-elicited activity in the BNST in a way that causes ELS mice to exhibit social deficits similar to those induced by BNST activation in non-stressed mice. Failing to find effects of BNST activation on social behavior While the complexity of social behavior necessitates arbitration from a number of brain regions (for reviews see Ko, 2017;Li & Dulac, 2018;Zoicas & Kornhuber, 2019), these findings back an idea that the BNST may integrate sensory with contextual information (Bjorni, Rovero, Yang, Holmes, & Halladay, 2020;Goode & Maren, 2017;Lebow & Chen, 2016)-in this case information related to novel conspecifics-to promote behavior appropriate for the given situation. Appropriate social behavioral responding for rodents may be influenced by a number of situational factors, such as the possibility for mating, predation, or establishment of hierarchy.…”

Cerebral Expression of Metabotropic Glutamate Receptor Subtype 5 in Idiopathic Autism Spectrum Disorder and Fragile X Syndrome: A Pilot Study

“…The deficits of FMRP in fmr1 KO mouse models result in dysfunction of crucial group 1 metabotropic glutamatergic pathways leading to dysregulated downstream signaling cascades including the mammalian target of rapamycin (mTOR) and the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK) pathways [ 17 ]. The correction of mGluR-LTD and behavioral symptoms in fmr1 KO mouse models suggests that the a biomarker to measure mGluR 5 expression in the living human brain represents a means to apply precision molecular medicine to ameliorate behavioral symptoms of FXS and possibly other subtypes of ASD [ 9 , 10 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ].…”