Role of central calcitonin gene-related peptide (CGRP) in locomotor and anxiety- and depression-like behaviors in two mouse strains exhibiting a CGRP-dependent difference in thermal pain sensitivity

J Mol Neurosci. 2009 Sep;39(1-2):125-36. doi: 10.1007/s12031-009-9201-z. Epub 2009 Apr 18.


We have previously shown that, in AKR and C57BL/6 mice, a genetic polymorphism results in differential expression of the peptide, calcitonin gene-related polypeptide (CGRP), explaining a strain difference in thermal pain sensitivity. Although CGRP is widely distributed in the brain, little is known about the effects of supraspinal CGRP. We used AKR and C57BL/6 mice as a model to explore the effects of centrally (intracerebroventricular) injected CGRP and the CGRP receptor antagonists, CGRP(8-37) and BIBN4096BS, in a series of behavioral assays. Locomotor activity was significantly increased in C57BL/6 mice following the injection of BIBN4096BS and in both strains after the administration of CGRP(8-37) into the third ventricle. CGRP increased paw-withdrawal latencies in C57BL/6 mice only, while decreasing depression-like behaviors in both strains in the forced-swimming test. CGRP and CGRP receptor antagonists failed to modulate activity in the elevated plus maze, a model of anxiety. Taken together, these results suggest a complex role for supraspinal CGRP systems in the regulation of locomotion, nociception, and depression-like behaviors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anxiety / metabolism*
  • Behavior, Animal / physiology*
  • Calcitonin Gene-Related Peptide / genetics
  • Calcitonin Gene-Related Peptide / metabolism*
  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Depression / metabolism*
  • Hot Temperature
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / physiology*
  • Neuropsychological Tests
  • Pain / physiopathology*
  • Pain Measurement
  • Polymorphism, Genetic
  • Receptors, Calcitonin Gene-Related Peptide / metabolism


  • Calcitonin Gene-Related Peptide Receptor Antagonists
  • Receptors, Calcitonin Gene-Related Peptide
  • Calcitonin Gene-Related Peptide