Dataset Information

Pituitary adenylate cyclase-activating polypeptide (PACAP) in the central nucleus of the amygdala induces anxiety via melanocortin receptors.

ABSTRACT: RATIONALE:Anxiety disorders are the most common mental disorders in the USA. Characterized by feelings of uncontrollable apprehension, they are accompanied by physical, affective, and behavioral symptoms. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor PAC1 (PAC1R) are highly expressed in the central nucleus of the amygdala (CeA), and they have gained growing attention for their proposed role in mediating the body's response to stress. OBJECTIVES:The aim of this study was to evaluate the anxiogenic effects of PACAP in the CeA and its effects on the hypothalamic-pituitary-adrenal (HPA) axis. Furthermore, the mechanism of action of PACAP in the CeA was investigated. METHODS:PACAP was microinfused into the CeA of rats, and its effects in the elevated plus maze (EPM), the defensive withdrawal tests, and plasma corticosterone levels were evaluated. The ability of the melanocortin receptor antagonist SHU9119 to block PACAP effect in the EPM was assessed. RESULTS:Intra-CeA PACAP exerted a dose-dependent anxiogenic effect and activated the HPA axis. In contrast, PACAP microinfused into the basolateral nucleus of the amygdala (BlA) had no effect. Finally, the anxiogenic effect of intra-CeA PACAP was prevented by SHU9119. CONCLUSIONS:These data prove an anxiogenic role for the PACAP system of the CeA and reveal that the melanocortin receptor 4 (MC4R) system of CeA mediates these effects. Our data provide insights into this neuropeptide system as a mechanism for modulating the behavioral and endocrine response to stress and suggest that dysregulations of this system may contribute to the pathophysiology of anxiety-related disorders.

SUBMITTER: Iemolo A

PROVIDER: S-EPMC4982769 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Pituitary adenylate cyclase-activating polypeptide (PACAP) in the central nucleus of the amygdala induces anxiety via melanocortin receptors.

Iemolo Attilio A Seiglie Mariel M Blasio Angelo A Cottone Pietro P Sabino Valentina V

Psychopharmacology 20160704 17

<h4>Rationale</h4>Anxiety disorders are the most common mental disorders in the USA. Characterized by feelings of uncontrollable apprehension, they are accompanied by physical, affective, and behavioral symptoms. The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP) and its receptor PAC1 (PAC1R) are highly expressed in the central nucleus of the amygdala (CeA), and they have gained growing attention for their proposed role in mediating the body's response to stress.<h4>Obje ...[more]

PMID: 27376948

Similar Datasets

Project description:Pituitary adenylate cyclase activating polypeptide (PACAP) is a well-conserved neuropeptide characteristic of vertebrates. This pluripotent hypothalamic neuropeptide regulates neurotransmitter release, intestinal motility, metabolism, cell division/differentiation, and immunity. In vertebrates, PACAP has a specific receptor (PAC1) but it can also activate the Vasoactive Intestinal Peptide receptors (VPAC1 and VPAC2). The evolution of the vertebrate PACAP ligand - receptor pair has been well-described. In contrast, the situation in invertebrates is much less clear. The PACAP ligand - receptor pair in invertebrates has mainly been studied using heterologous antibodies raised against mammalian peptides. A few partial PACAP cDNA clones sharing >87% aa identity with vertebrate PACAP have been isolated from a cnidarian, several protostomes and tunicates but no gene has been reported. Moreover, current evolutionary models of the peptide and receptors using molecular data from phylogenetically distinct invertebrate species (mostly nematodes and arthropods) suggests the PACAP ligand and receptors are exclusive to vertebrate genomes. A basal deuterostome, the cephalochordate amphioxus (Branchiostoma floridae), is the only invertebrate in which elements of a PACAP-like system exists but the peptides and receptor share relatively low sequence conservation with the vertebrate homolog system and are a hybrid with the vertebrate glucagon system. In this study, the evolution of the PACAP system is revisited taking advantage of the burgeoning sequence data (genome and transcriptomes) available for invertebrates to uncover clues about when it first appeared. The results suggest that elements of the PACAP system are absent from protozoans, non-bilaterians, and protostomes and they only emerged after the protostome-deuterostome divergence. PACAP and its receptors appeared in vertebrate genomes and they probably shared a common ancestral origin with the cephalochordate PACAP/GCG-like system which after the genome tetraploidization events that preceded the vertebrate radiation generated the PACAP ligand and receptor pair and also the other members of the Secretin family peptides and their receptors.

Dataset Information

Pituitary adenylate cyclase-activating polypeptide (PACAP) in the central nucleus of the amygdala induces anxiety via melanocortin receptors.

Publications

Pituitary adenylate cyclase-activating polypeptide (PACAP) in the central nucleus of the amygdala induces anxiety via melanocortin receptors.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets