VASOPRESSINERGIC PROJECTION FROM THE PARAVENTRICULAR NUCELUS TO THE CENTRAL AMYGDALA MODULATE SOCIAL INTERACTION AND ANXIETY IN RATS

Arginine vasopressin (AVP) is a hypothalamic neuropeptide hormone that, beyond its well-known peripheral effects (e.g. vasoconstriction and antidiuresis), plays an important role in the regulation of complex behaviors. AVP-expressing neurons in the paraventricular nucleus of the hypothalamus (PVN) project to several limbic regions, including the central nucleus of the amygdala (CeA), a key structure involved in emotional and social processing. Here, we investigated the behavioral role of the vasopressinergic PVN projection to the CeA. Using AVP-Cre transgenic rats, we chemogenetically activated or inhibited PVN–CeA projections several weeks after bilateral intra-PVN injection of adeno-associated viral vectors and bilateral intra-CeA cannula implantation. Clozapine-N-oxide (CNO; 1 mM/0.4 µl) was administered 30 min before behavioral testing, including the three-chamber sociability test, open field, elevated plus maze, and marble burying test. Animals were transcardially perfused 2 h after CNO administration to verify injection sites and assess neuronal activation using c-Fos immunohistochemistry. C-Fos expression patterns confirmed effective pathway-specific chemogenetic manipulation. Activation of PVN–CeA projections using excitatory DREADDs significantly increased the sociability index, whereas inhibition of this pathway markedly reduced social interaction. Control viral constructs showed no effect on social behavior following saline or CNO administration. Increased vasopressinergic tone in the CeA elevated anxiety-related parameters, while inhibition produced anxiolytic effects. These findings indicate that the PVN–amygdala vasopressinergic pathway facilitates social behavior despite exerting anxiogenic effects, providing insight into neural mechanisms underlying social regulation and potential targets for social dysfunction.