Year: 2025
Type: article
Abstract: Sex differences in responsiveness to social stress in adulthood are highly conserved across species, with females more sensitive to isolation. Here, we show that Arginine vasopressin receptor 1a (AVPR1A) in the central nucleus of the amygdala (CeA) mediates the enhanced susceptibility of females to post-pubertal chronic social isolation stress (CSIS) in mice. Chemogenetic activation of AVPR1ACeA circuits induces anxiety-related behaviors in both sexes. However, genetic, pharmacological, chemogenetic and optogenetic loss of function approaches support the idea that it is only endogenously engaged in females in the context of CSIS. Using a combination of virus-based tools, we identified a major source of AVP ligand in the posterodorsal part of the medial amygdala (MePD) as well as an important downstream target of AVPR1ACeA neurons, the dorsolateral striatum (DLS). Loss of function approaches identified three nodes in the circuit that provide sex-specificity in the effects of CSIS on anxiety-related behaviors: 1) ERα signaling in AVPMePD neurons; 2) engagement of the AVPR1A pathway in the CeA; and 3) number of AVPR1ACeA projections to the DLS. These data support new therapeutic applications for AVPR1A antagonists in women experiencing social isolation or loneliness. Females are more sensitive to social exclusion and loneliness, risk factors for anxiety and stressrelated disorders. Here, the authors identified molecular signals in the amygdala that make females more susceptible to effects of chronic social isolation in mice.
Source: Nature Communications
Authors: Marie François, Kelly L. Vranich, Isabella Canal Delgado, Alexandre Lafond, Natalie R. Lopatinsky, Tronjay Davis, Eastman M. Lewis, Mia Kuromaru, Rim Hassouna, Brenna Williams, Sebastian E. Ho, Lucas A. C. Souza, Daniele Neri, Youjin Oh, Christopher D. Makinson, Kevin G. Bath, Gül Dölen, Lori M. Zeltser
Institutions: Columbia University Irving Medical Center, National Institutes of Health, Johns Hopkins University, Johns Hopkins Medicine, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Columbia University, New York State Psychiatric Institute, University of California, Berkeley
Language: English
Subfield: Social Psychology
Field: Psychology
Domain: Social Sciences
Open Access status: gold
Estimated APC paid: $6,990
Funders: U.S. Department of Health and Human Services, Klarman Family Foundation, University of Michigan, Russell Berrie Foundation, National Institutes of Health, Michigan Diabetes Research Center, University of Michigan, National Institute of Mental Health, National Cancer Institute, National Institute of Diabetes and Digestive and Kidney Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: G1847454291, G2614766610, G301048564, G4246341217, Characterization of the role of Fmr1 in oxytocin neuronal subtypes, G5039347226, Diabetes and Endocrinology Research Center, G5317523162, G6341612086, G643119639, Functional mapping of arginine vasopressin receptor 1A circuits that promote anorexic behavior, G9000025502, G9000091460, Diabetes Research Center, Cancer Center Support Grant
OpenAlex ID: W4415880753