A current major focus of the laboratory is investigation of the physiological function of the neuropeptide tuberoinfundibular peptide of 39 residues (TIP39) and its receptor the parathyroid hormone 2 (PTH2) receptor, which were discovered in this laboratory several years ago. Using site directed mutagenesis and bacterial expression we developed a highly selective and potent peptide antagonist of the PTH2 receptor. We have completed an in vitro characterization of the antagonist and are now ready to proceed with experiments using it in living animals. We are in the midst of a series of experiments aimed at identifying the situations and stimuli that lead to activation of the TIP39-PTH2 receptor system. One completed experiment that uses immunohistochemical colocalization of the immediate early gene c-fos and TIP39 demonstrates that TIP39 containing neurons are activated in association with male sexual behavior. We have obtained mice with genetic replacement of the gene for TIP39 by a marker gene. We have performed a comprehensive study of the distribution of TIP39 and a detailed comparison with the distribution of the PTH2 receptor in mouse brain using these transgenic mice. Based on the presence of TIP39 and the PTH2 receptor in brain regions involved in emotional function we have created TIP39 null mice and initiated a set of experiments comparing the behavior of wild-type and TIP39 knockout mice with a focus on anxiety-related behaviors.