title: Calcitonin gene-related peptide in the bed nucleus of the stria terminalis produces an anxiety-like pattern of behavior and increases neural activation in anxiety-related structures.
abstract: Calcitonin gene-related peptide (CGRP) evokes anxiety-like responses when infused into the lateral ventricle of rats. Because the bed nucleus of the stria terminalis (BNST) lies immediately adjacent to the lateral ventricle, is rich in CGRP receptors, and has itself been implicated in anxiety, we evaluated the hypothesis that these effects are attributable to stimulation of CGRP receptors within the BNST itself. Bilateral intra-BNST, but not dorsal, CGRP infusions (0, 200, 400, 800 ng/side) enhanced startle amplitude in a dose-dependent manner, and produced an anxiety-like response on the elevated plus maze. Intra-BNST infusion of the CGRP antagonist, αCGRP(8-37), blocked the effect of CGRP on startle, and also blocked startle potentiation produced by exposure to trimethylthiazoline (a component of fox feces that induces anxiety-like behavior in rats). Intra-BNST, but not dorsal, CGRP infusions also increased c-Fos immunoreactivity in a number of anxiety-related brain areas (central nucleus of the amygdala, locus ceruleus, ventrolateral septal nucleus, paraventricular hypothalamic nucleus, lateral hypothalamus, lateral parabrachial nucleus, dorsal raphe nucleus, and nucleus accumbens shell), all of which receive direct projections from the BNST. Together, the results indicate that the activation of BNST CGRP receptors is both necessary and sufficient for some anxiety responses and that these effects may be mediated by activation of a wider network of BNST efferent structures. If so, inhibition of CGRP receptors may be a clinically useful strategy for anxiety reduction.
authors.affiliation: Department of Psychiatry, Yerkes National Primate Center, Emory University, Atlanta, Georgia 30329, USA. ksink@emory.edu
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Sink
authors.forename: David L
authors.initials: DL
authors.lastname: Walker
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Michael
authors.initials: M
authors.lastname: Davis
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000679:Amygdala / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000378:metabolism* / Q000523:psychology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002452:Cell Count; D004525:Efferent Pathways / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D008125:Locus Coeruleus / Q000378:metabolism; D008297:Male; D018782:Maze Learning; D008845:Microinjections; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism; D013216:Reflex, Startle; D012686:Septal Nuclei / Q000187:drug effects / Q000378:metabolism*; D013844:Thiazoles / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: C451263:2,4,5 trimethylthiazoline; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D016760:Proto-Oncogene Proteins c-fos; D018015:Receptors, Calcitonin Gene-Related Peptide; D013844:Thiazoles; D015740:Calcitonin Gene-Related Peptide