title: CRF mediates the anxiogenic and anti-rewarding, but not the anorectic effects of PACAP.
abstract: 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 receptor antagonist D-Phe-CRF(12-41). Interestingly, the CRF antagonist had no effect on PACAP-induced increased plasma corticosterone, reduction of food intake, and body weight loss. Finally, we found that PACAP increased CRF levels in the paraventricular nucleus of the hypothalamus and, importantly, in the central nucleus of the amygdala, as measured by solid phase radioimmunoassay and quantitative real-time PCR. Our results strengthen the notion that PACAP is a strong mediator of the behavioral response to stress and prove for the first time that this neuropeptide has anti-rewarding (ie, pro-depressant) effects. In addition, we identified the mechanism by which PACAP exerts its anxiogenic and pro-depressant effects, via the recruitment of the central CRF system and independently from HPA axis activation.
authors: Laboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors: Riccardo
authors: R
authors: Dore
authors: Attilio
authors: A
authors: Iemolo
authors: Karen L
authors: KL
authors: Smith
authors: Xiaofan
authors: X
authors: Wang
authors: Pietro
authors: P
authors: Cottone
authors: Valentina
authors: V
authors: Sabino
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000097:blood / Q000139:chemically induced* / Q000503:physiopathology; D001835:Body Weight / Q000187:drug effects; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000378:metabolism / Q000502:physiology*; D004435:Eating / Q000187:drug effects; D057967:Infusions, Intraventricular; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010455:Peptides / Q000494:pharmacology; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D012201:Reward; D012653:Self Stimulation / Q000187:drug effects
chemical_list: D010455:Peptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D018019:Receptors, Corticotropin-Releasing Hormone; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone
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