Enhanced social reward response and anxiety-like behavior with downregulation of nucleus accumbens glucocorticoid receptor in BALB/c mice

• Published in: Journal of Veterinary Medical Science Vol. 85; no. 1; pp. 30 - 39
• Main Authors: CHIBA, Shuichi, NUMAKAWA, Tadahiro, MURATA, Takuya, KAWAMINAMI, Mitsumori, HIMI, Toshiyuki
• Format: Journal Article
• Language: English
• Published: Japan JAPANESE SOCIETY OF VETERINARY SCIENCE 01.01.2023; Japan Science and Technology Agency; The Japanese Society of Veterinary Science
• Subjects: Anhedonia; Animals; Anxiety; Behavior; Behavior, Animal - physiology; depression; Down-Regulation; glucocorticoid receptor; Glucocorticoids; Hedonic response; Huddling; Male; Mental disorders; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Neurotrophic factors; Nucleus accumbens; Nucleus Accumbens - metabolism; Open-field behavior; Physiology; Place preference conditioning; Receptors, Glucocorticoid - metabolism; Reinforcement; Reward; Saccharin; Social Behavior; Social interaction; Social interactions; social reward; Stress, Psychological - complications; Stress, Psychological - metabolism; Western blotting; anxiety; glucocorticoid receptor; depression; nucleus accumbens; social reward; anhedonia
• ISSN: 0916-7250; 1347-7439
• DOI: 10.1292/jvms.22-0103

Social anhedonia is a psychological state with difficulty in experiencing pleasure from social interactions and is observed in various diseases, such as depressive disorders. Although the relationships between social reward responses and anxiety- and depression-like behaviors have remained unclear, a social reward conditioned place preference (SCPP) test can be used to analyze the rewarding nature of social interactions. To elucidate these relationships, we used 5-week-old male mice of AKR, BALB/c, and C57BL/6J strains and conducted behavioral tests in the following order: elevated plus-maze test (EPM), open field test (OFT), SCPP, saccharin preference test (SPT), and passive avoidance test. The nucleus accumbens of these mice were collected 24 hr after these behavioral tests and were used for western blotting to determine the levels of receptors for brain-derived neurotrophic factors and glucocorticoids. BALB/c mice displayed the highest levels of anxiety-like behavior in EPM and OFT as well as physical anhedonia-like behaviors in SPT. They also showed increased responses to social rewards and huddling behaviors in SCPP, with downregulated glucocorticoid receptor (GR). Regression analysis results revealed positive influences of anxiety- and physical anhedonia-like behaviors and expressions of GR on social reward responses. Collectively, temperament associated with anxiety and physical anhedonia may affect social reward responses, which possibly is influenced by the expression of GR that can modify these psychological traits.