title: Pituitary Adenylate Cyclase-Activating Peptide in the Central Amygdala Causes Anorexia and Body Weight Loss via the Melanocortin and the TrkB Systems.
abstract: Growing evidence suggests that the pituitary adenylate cyclase-activating polypeptide (PACAP)/PAC1 receptor system represents one of the main regulators of the behavioral, endocrine, and autonomic responses to stress. Although induction of anorexia is a well-documented effect of PACAP, the central sites underlying this phenomenon are poorly understood. The present studies addressed this question by examining the neuroanatomical, behavioral, and pharmacological mechanisms mediating the anorexia produced by PACAP in the central nucleus of the amygdala (CeA), a limbic structure implicated in the emotional components of ingestive behavior. Male rats were microinfused with PACAP (0-1 μg per rat) into the CeA and home-cage food intake, body weight change, microstructural analysis of food intake, and locomotor activity were assessed. Intra-CeA (but not intra-basolateral amygdala) PACAP dose-dependently induced anorexia and body weight loss without affecting locomotor activity. PACAP-treated rats ate smaller meals of normal duration, revealing that PACAP slowed feeding within meals by decreasing the regularity and maintenance of feeding from pellet-to-pellet; postprandial satiety was unaffected. Intra-CeA PACAP-induced anorexia was blocked by coinfusion of either the melanocortin receptor 3/4 antagonist SHU 9119 or the tyrosine kinase B (TrKB) inhibitor k-252a, but not the CRF receptor antagonist D-Phe-CRF(12-41). These results indicate that the CeA is one of the brain areas through which the PACAP system promotes anorexia and that PACAP preferentially lessens the maintenance of feeding in rats, effects opposite to those of palatable food. We also demonstrate that PACAP in the CeA exerts its anorectic effects via local melanocortin and the TrKB systems, and independently from CRF.
authors: 1] Laboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA [2] Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors: Attilio
authors: A
authors: Iemolo
authors: 1] Laboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA [2] Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors: Antonio
authors: A
authors: Ferragud
authors: 1] Laboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA [2] Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors: Pietro
authors: P
authors: Cottone
authors: 1] Laboratory of Addictive Disorders, Department of Pharmacology and Experimental Therapeutics, Boston University School of Medicine, Boston, MA, USA [2] Department of Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors: Valentina
authors: V
authors: Sabino
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000855:Anorexia / Q000139:chemically induced*; D001835:Body Weight / Q000187:drug effects*; D066274:Central Amygdaloid Nucleus / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D008297:Male; D053486:Melanocortins / Q000378:metabolism*; D009074:Melanocyte-Stimulating Hormones / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism*; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D053486:Melanocortins; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D014665:Vasodilator Agents; C113202:phenylalanyl corticotropin-releasing factor (12-41); C103272:SHU 9119; D009074:Melanocyte-Stimulating Hormones; D003346:Corticotropin-Releasing Hormone; D020813:Receptor, trkB
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