Prolactin-releasing peptide (PrRP) is expressed in three neuronal populations in the brain: the ventrolateral medulla (VLM), nucleus of the tractus solitarius (NTS) and dorsomedial hypothalamus (DMH) [1]. The receptor for PrRP, GPR10, is expressed at various sites involved in appetite and autonomic regulation. Mice with a conditional knock out for the PrRP peptide (loxSTOPlox [LSL]-Prrp) and those with a null mutation in the GPR10 receptor (Gpr10-/-) have a late-stage obese phenotype and are hyperphagic [1,2]. In studies using rats, central injection of PrRP increased mean arterial blood pressure (MAP) [3], while hypotensive haemorrhage increased c-Fos expression in PrRP neurones of the VLM and NTS [4]. Baseline blood pressure (BP) recordings were made in conscious, pre-obese LSL-Prrp and Gpr10-/- mice, using tail-cuff plethysmography, and hypotension was induced by the drug, clonidine (intraperitoneal (IP), 0.1mg/kg). Tracing studies were performed using Prrp-cre::EYFP mice injected with cre-dependent anterograde tracer, AAV-h134r-mCherry, into the VLM. All surgery was performed under anaesthesia with isoflurane (induction 3%; maintenance 1-2%). Mice were later perfused with 4% paraformaldehyde under anaesthesia. Immunohistochemistry using DsRed and EYFP antibodies verified transduction of PrRPVLM neurones. All results given are mean±SEM; unpaired t-test. Gpr10-/- (n=5) mice exhibit significantly lower baseline MAP than wild-type (WT) (n=8) counterparts (66±4mmHg vs 100±9mmHg; p<0.005). When injected with a low dose of clonidine, BP was too low to record by tail-cuff. LSL-Prrp (n=6) mice exhibit no difference in baseline MAP compared with WT (n=8) mice (99±9mmHg vs 101±7mmHg). However, when given IP clonidine, LSL-PrRP (n=6) mice were unable to defend their BP under hypotensive challenge, compared with WT (n=9) (relative change in MAP (-23±4mmHg vs -9±2mmHg; p<0.005). Anterograde tracing revealed projections to the bed nucleus of the stria terminalis (BNST), paraventricular hypothalamic nucleus (PVH), DMH, periaqueductal grey (PAG) and dorsal vagal complex. Projections to the BNST, PVH, and PAG were confirmed by retrograde tracing in Prrp-cre::EYFP mice. These results demonstrate that PrRP and GPR10 are involved in cardiovascular regulation. The location of PrRPVLM neurones means that they are likely to be involved in mediating this role. In this study we have shown that PrRPVLM neurones have strong projections to regions of the brain with known roles in cardiovascular regulation, providing further support to this assertion.