Activation of Limbic and Mesolimbic Pathways in the Brain by Arginine-vasopressin: Roles in Social Behavior, Psychosocial Stress, and Cardiovascular Disease

Arginine-vasopressin (AVP) is a nonapeptide that is produced in the hypothalamus and regulates social behavior and communication. A major goal of our research program is to develop a psychosocial stress model to test the hypothesis that AVP may have therapeutic potential for psychosocial stress-associated conditions, including cardiovascular disease and neuropsychiatric disorders. Based on previous work by our team and other investigators, our data indicate that AVP acts in the anterior hypothalamic area (AHA), a node in the limbic system, to stimulate aggression and flank marking, a type of social communication, in the Syrian hamster ( Mesocricetus auratus ). It is not clear if AVP influences other behaviors that are associated with stimulation of the sympathetic nervous system. Therefore, the present study was designed to address this knowledge gap. In the present study, stereotaxic surgeries were performed to cannulate four adult male and four adult female hamsters with cannulae aimed at the AHA. Cannulated animals were microinjected with 200 nl of a 9 µM AVP solution and saline in counterbalanced order with a 4-day inter-test interval, and their behavioral responses to AVP were also quantified. Flank marking data was collected for all 8 subjects, and AVP in the AHA significantly increased the occurrence of flank marking (χ 2 (1, N=8)= p<0.05), replicating previous findings. Additional behavioral measures were collected for the four males. Results of paired samples t-tests indicate that AVP in the AHA significantly increased the duration (t(3)=2.198, p<0.05) and frequency (t(3)=2.744, p<0.05) of intense flank grooming, and also increased general body grooming behavior (t(3)=2.580, p<0.05). Other behaviors appeared to increase as well (e.g., body shakes, paw liking), but the effects were not statistically significant. Taken together, it is known that AVP in the AHA regulates social behavior and communication, and our data suggest that AVP may also act in the AHA to stimulate the sympathetic nervous system and behavioral arousal. We propose that activation of the AHA by AVP stimulates other brain areas, directly and indirectly, that are part of the limbic and mesolimbic systems, which play a role in regulating responses to psychosocial stressors. Future studies will explore sex differences and AVP effects on cardiovascular responses in the context of social behavior and psychosocial stress. Our long-term goal is to build on these preliminary findings to determine whether AVP may regulate psychosocial stress-induced over reactivity of the sympathetic nervous system and myocardial injury (in animal CVD models), a first step in exploring heart-brain interactions that may link psychosocial stress with negative cardiovascular disease outcomes. This project is funded by NIH grant #1K01HL145339-01A1 (PI: M. Gil). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.