{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n The arginine vasopressin receptor 1B (AVPR1B) has emerged as a multifaceted mediator central to both behavioral and neuroendocrine regulation. In the central nervous system, studies using knockout animal models demonstrate that AVPR1B is crucial for the modulation of social behaviors; for example, mice lacking AVPR1B display markedly reduced intermale and maternal aggression, impaired social and olfactory recognition, and altered patterns of ultrasonic vocalizations. These findings, together with evidence of its enriched expression in the hippocampal CA2 pyramidal neurons—an area implicated in processing social cues—support a role for AVPR1B in the formation, retrieval, and appropriate behavioral responding to socially relevant information."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In its neuroendocrine role, AVPR1B expressed on anterior pituitary corticotrophs plays a key part in stimulating adrenocorticotropic hormone (ACTH) release under both basal conditions and in response to acute or chronic stress. This contributes directly to the proper function of the hypothalamic–pituitary–adrenal (HPA) axis, linking AVPR1B activity with stress responsiveness and glucocorticoid regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its central actions, AVPR1B influences peripheral metabolic regulation. Animal studies indicate that deletion or genetic variation in AVPR1B improves insulin sensitivity, modifies lipid metabolism, and is associated with overweight and diabetes mellitus, suggesting that signaling via this receptor contributes to energy homeostasis and metabolic health."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "15", "end_ref": "18"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n At the genetic and molecular levels, common polymorphisms in the AVPR1B gene have been linked to variations in susceptibility to psychiatric conditions such as panic disorder, major depression, and other stress‐related mood disorders, highlighting its potential as a therapeutic target in psychiatric care."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "19", "end_ref": "23"}]}, {"type": "t", "text": "\n Moreover, AVPR1B receptors are capable of forming both homo‐ and heterodimers (for instance with the corticotropin‐releasing hormone receptor CRHR1), potentially modifying their signaling properties and impact on stress responsivity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "24"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, AVPR1B has been implicated in other contexts: it may facilitate receptor‐mediated endocytosis events that are exploited by pathogens such as SARS‐CoV‑2 during cellular entry"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "25"}]}, {"type": "t", "text": ", while alterations in AVPR1B expression have been observed in corticotroph adenomas associated with Cushing’s disease, linking aberrant receptor regulation to hypercortisolemia."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "26", "end_ref": "29"}]}, {"type": "t", "text": " Furthermore, modulation of AVPR1B signaling has been found to influence morphine tolerance, suggesting broader implications in pain management and addiction."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "30"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies underscore that AVPR1B serves as a critical nexus between social behavior, stress responsiveness, and metabolic regulation. Its diverse roles—ranging from coupling social cue processing in the hippocampus to facilitating ACTH secretion in the pituitary, as well as modulating energy balance peripherally—render it a promising candidate for targeted interventions in psychiatric, metabolic, and stress‐related disorders.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "S R Wersinger, E I Ginns, A-M O'Carroll, et al. 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