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.
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.
Schorscher-Petcu
Ara
A
Department of Neurology and Neurosurgery, McGill University, Montreal, Canada.
Austin
Jean-Sébastien
JS
Mogil
Jeffrey S
JS
Quirion
Rémi
R
D000818:Animals; D001007:Anxiety / Q000378:metabolism*; D001522:Behavior, Animal / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D003863:Depression / Q000378:metabolism*; D006358:Hot Temperature; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000502:physiology*; D009483:Neuropsychological Tests; D010146:Pain / Q000503:physiopathology*; D010147:Pain Measurement; D011110:Polymorphism, Genetic; D018015:Receptors, Calcitonin Gene-Related Peptide / Q000378:metabolism
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D018015:Receptors, Calcitonin Gene-Related Peptide; D015740:Calcitonin Gene-Related Peptide