Dataset for Figures 2 & 3

<b>Background:</b> Alcohol use disorder (AUD) remains a significant global health challenge, necessitating the exploration of novel pharmacotherapeutic interventions. Our recent study observed that intranasal (IN) administration of arginine vasopressin (AVP) decreases voluntary consumption of sweetened ethanol (EtOH) in mice, a promising development, given than IN AVP does not affect the blood pressure or stress responses associated with systemic AVP administration. To further characterize AVP’s potential to regulate alcohol drinking, here we investigated the effects of IN AVP on voluntary intake of unsweetened ethanol (EtOH) in both single and group housed mice, and the involvement of AVP receptors (V1a, V1b) and oxytocin receptors (Oxtr).<b>Methods:</b> C57BL/6J mice were used in a two-bottle choice (2BC) paradigm to assess voluntary EtOH consumption. Experiment 1 examined single housed mice, while Experiment 2 used group housed mice in automated HM2 cages. Mice received IN injections of AVP (1.0 or 3.0 mg/kg) with or without pretreatment of AVP V1a, V1b, or Oxtr antagonists.<b>Results:</b> IN AVP (1.0 mg/kg) decreased voluntary EtOH intake in single housed mice, an effect attenuated by pretreatment with Avpr1a, Avpr1b, or Oxtr antagonists. A higher dose of AVP (3.0 mg/kg) also inhibited EtOH intake in single housed mice, and this effect was blocked specifically by the Avpr V1a receptor antagonist SR-49059. In group housed mice, IN AVP (3.0 mg/kg) decreased EtOH intake, an effect blocked by either the V1a receptor antagonist or V1b antagonist.<b>Conclusions:</b> IN AVP decreases voluntary EtOH intake in both single and group housed mice. The suppressive effects of IN AVP are mediated by V1a receptors in single housed mice, while both V1a and V1b receptors are involved in group housed mice. These findings suggest IN AVP may be a potential therapeutic target for AUD, warranting further investigation in preclinical models of excessive alcohol drinking and in human subjects.