CNS glucagon-like peptide-1 receptors mediate endocrine and anxiety responses to interoceptive and psychogenic stressors.
Responses to stressors serve to adjust physiology and behavior to increase short-term survival at the potential expense of increasing susceptibility to disease over the long term. We show that glucagon-like peptide-1 (7-36) amide (GLP-1) increases levels of the stress-activated hormones ACTH and corticosterone when administered directly into the rat brain and increases levels of anxiety as measured by the elevated plus maze. The endocrine response is preferentially activated by GLP-1 administration in the paraventricular nucleus of the hypothalamus, whereas the anxiety response is preferentially activated by administration in the central nucleus of the amygdala. Furthermore, GLP-1 antagonists block increases in stress hormones associated with the toxin LiCl and both the endocrine and anxiety responses to vertical heights. Although diverse neural circuits must necessarily process disparate stressors, the current data implicate a role for the GLP-1 system as a critical mediator of multiple stress responses.
Kinzig
Kimberly P
KP
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA. kkinzig1@jhmi.edu
D'Alessio
David A
DA
Herman
James P
JP
Sakai
Randall R
RR
Vahl
Torsten P
TP
Figueiredo
Helmer F
HF
Murphy
Erin K
EK
Seeley
Randy J
RJ
Figueredo
Helmer F
HF
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D002404:Catheterization; D002490:Central Nervous System / Q000378:metabolism*; D003345:Corticosterone / Q000097:blood; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D004703:Endocrine System / Q000378:metabolism*; D005934:Glucagon; D052216:Glucagon-Like Peptide 1; D000067757:Glucagon-Like Peptide-1 Receptor; D004763:Glucagon-Like Peptides; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000008:administration & dosage; D010913:Pituitary-Adrenal System / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D018027:Receptors, Glucagon / Q000378:metabolism*; D013315:Stress, Psychological / Q000378:metabolism*
C000593835:Glp1r protein, rat; D000067757:Glucagon-Like Peptide-1 Receptor; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; D018027:Receptors, Glucagon; C055453:glucagon-like peptide 1 (7-36)amide; C104416:astressin; D004763:Glucagon-Like Peptides; D052216:Glucagon-Like Peptide 1; D000324:Adrenocorticotropic Hormone; D005934:Glucagon; D003346:Corticotropin-Releasing Hormone; D003345:Corticosterone