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Anxiety disorders represent the most common mental disturbances in the world, and they are characterized by an abnormal response to stress. Pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor PAC1 have been proposed to have a key role in mediating the responses to stress as well as the regulation of food intake and body weight. Corticotropin-releasing factor (CRF), the major stress peptide in the brain, has been hypothesized to be involved in PACAP effects, but the reports are conflicting so far. The present study was aimed at further characterizing the behavioral effects of PACAP in rats and at determining the role of central CRF receptors. We found that intracerebroventricular PACAP treatment induced anxiety-like behavior in the elevated plus maze test and elevated intracranial self-stimulation thresholds; both of these effects were fully blocked by concurrent treatment with the CRF …