The present study surveyed activation of central neurons following peripheral administration of apelin-12 (AP12), an apelin peptide homologue, by examining the distribution of neurons expressing c-Fos protein. AP12 is known to induce gastric acid secretion among other physiological functions such as regulation of circulation. It was recently reported that apelin counteracted the effect of arginine vasopressin (AVP) in the maintenance of body fluid homeostasis. We attempted to clarify which neurons in the central nervous system express c-Fos protein after intraperitoneal injection of AP12. Intraperitoneally administered AP12 induced expression of c-Fos protein in several nuclei throughout the brain. In the paraventricular nucleus of the hypothalamus (PAH), lateral hypothalamic area (LH), paraventricular nucleus of the thalamus (PVT), periaqueductal gray matter (PAG), bed nucleus of the stria terminalis (BNST), locus coeruleus (LC), lateral parabrachial nucleus (Pbl), the complex of the solitary tract nucleus (NTS) and dorsal motor nucleus of the vagus nerve (DMX), numbers of neurons expressing c-Fos protein were much higher in test than in control experiments. These findings suggest that AP12 stimulates central neurons that may play roles in the regulation of gastric acid, and hypothalamic neurons that may play roles in the maintenance of body fluid homeostasis as well as other physiological functions. (c) 2007 Elsevier Ireland Ltd. All rights reserved.