The purpose of the present studies was to investigate the function and possible clinical relevance of some neuropeptides. Thyrotropin-releasing hormone (TRH) has been suggested in the past to be involved in the mechanism of action of antidepressant compounds. In the present study, we found that repeated administration of either the tricyclic antidepressant desipramine (DMI) or the monoamine oxidase inhibitor nialamide reduced the ability of the TRH analog MK-771 (L-pyro-2-aminoadipyl-histidyl-thiazolidine-4-carboxamide) to induce wet-dog shakes in rats. These results are consistent with the idea that TRH systems are involved in the mechanism of action of antidepressant compounds. Calcitonin gene-related peptide (CGRP) content as well as CGRP receptors have been shown by our laboratory to be densely localized within the central amygdaloid nucleus (Ce). When CGRP was microinjected into this nucleus, significant increases in both blood pressure (BP) and heart rate (HR) occurred. These results provide a functional correlate for the presence of CGRP and its receptors in the Ce. Previous studies in our laboratory demonstrated that microinjection of atrial natriuretic peptide (ANP) into the preoptic suprachiasmatic nucleus (POSC) produced significant elevations in both BP and HR. The present studies investigated the mechanism of action of this response to ANP. The results from this study revealed that propranolol inhibited the ANP-induced rise in HR. In addition, atrial peptide fragment (13-28, rat) was found to produce similar changes in BP and HR over a similar time course as atriopeptin III (5-28). These results indicate that the portion of the atrial peptide 5-12 is not essential for central cardiovascular effects to occur, and that the effect on HR by ANP is mediated to some extent by Beta-adrenergic receptors.