期刊
NEUROPHARMACOLOGY
卷 58, 期 1, 页码 156-165出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2009.07.009
关键词
Calcitonin gene-related peptide (CGRP); CGRP receptor; Receptor activity-modifying protein 1 (RAMP1); Migraine; Photophobia
资金
- NCRR NIH HHS [UL1 RR024979] Funding Source: Medline
- NIDCR NIH HHS [R01 DE016511, DE018149, R21 DE018149, DE016511, R21 DE018149-02, R01 DE016511-17] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007337] Funding Source: Medline
- NINDS NIH HHS [T32 NS045549, T32 NS045449, T32 NS045549-06] Funding Source: Medline
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR024979] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DENTAL &CRANIOFACIAL RESEARCH [R21DE018149, R01DE016511] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [T32GM007337] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [T32NS045549] Funding Source: NIH RePORTER
Migraine is a complex neurological disorder with a significant impact on patients and society. Clinical and preclinical studies have established the neuropeptide calcitonin gene-related peptide (CGRP) as a key player in migraine and other neurovascular headaches. To study the role of CGRP in these disorders, we have characterized the photophobic phenotype of nestin/hRAMP1 mice, a transgenic model with genetically engineered increased sensitivity to CGRR These mice have increased nervous system expression of a regulatory subunit of the CGRP receptor, human receptor activity-modifying receptor (hRAMP1). We have previously demonstrated that nestin/hRAMP1 mice display a light-aversive behavior that is greatly enhanced by CGRP and blocked by a CGRP receptor antagonist used to treat migraine. Here we have compared their behavior in two different experimental setups with testing chambers of different sizes and light intensities as well as in complete darkness. We demonstrated similar degrees of light aversion in nestin/hRAMP1 mice with 1000 and 50 lux. To control for other possible factors driving nestin/hRAMP1 mice to the dark zone, we tested them in the absence of any light, and they showed identical behavior as littermates. Furthermore, both nestin/hRAMP1 and control mice have decreased motility in response to CGRP in the dark, but not the light side of the chamber. Our findings confirm the robust CGRP-induced light-aversive phenotype of nestin/hRAMP1 mice, which can be a surrogate of photophobia, and validates its usefulness as a model of migraine and other disorders associated with photophobia. (C) 2009 Elsevier Ltd. All rights reserved.
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