Journal article
Modulation of CGRP-Induced Light Aversion in Wild-Type Mice by a 5-HT1B/D Agonist
The Journal of neuroscience, Vol.32(44), pp.15439-15449
10/31/2012
DOI: 10.1523/JNEUROSCI.3265-12.2012
PMID: 23115181
Abstract
The neuropeptide calcitonin gene-related peptide (CGRP) plays a critical role in the pathophysiology of migraine. We have focused on the role of CGRP in photophobia, which is a common migraine symptom. We previously used an operant-based assay to show that CGRP-sensitized transgenic (
nestin/hRAMP1
), but not control, mice exhibited light aversion in response to an intracerebroventricular CGRP injection. A key question was whether the transgenic phenotype was due to overexpression of the CGRP receptor at endogenous or novel expression sites. We reasoned that if endogenous receptor sites were sufficient for light-aversive behavior, then wild-type mice should also show the phenotype when given a sufficiently strong stimulus. In this study, we report that mice with normal levels of endogenous CGRP receptors demonstrate light avoidance following CGRP administration. This phenotype required the combination of two factors: higher light intensity and habituation to the testing chamber. Control tests confirmed that light aversion was dependent on coincident exposure to CGRP and light and cannot be fully explained by increased anxiety. Furthermore, CGRP reduced locomotion only in the dark, not in the light. Coadministration of rizatriptan, a 5-HT
1B/D
agonist anti-migraine drug, attenuated the effects of exogenous CGRP on light aversion and motility. This suggests that triptans can act by mechanisms that are distinct from inhibition of CGRP release. Thus, we demonstrate that activation of endogenous CGRP receptors is sufficient to elicit light aversion in mice, which can be modulated by a drug commonly used to treat migraine.
Details
- Title: Subtitle
- Modulation of CGRP-Induced Light Aversion in Wild-Type Mice by a 5-HT1B/D Agonist
- Creators
- Eric A Kaiser - Department of Molecular Physiology and Biophysics andAdisa Kuburas - Department of Molecular Physiology and Biophysics andAna Recober - Department of Neurology, University of Iowa, Iowa City, Iowa 52242, andAndrew F Russo - Department of Molecular Physiology and Biophysics and
- Resource Type
- Journal article
- Publication Details
- The Journal of neuroscience, Vol.32(44), pp.15439-15449
- DOI
- 10.1523/JNEUROSCI.3265-12.2012
- PMID
- 23115181
- NLM abbreviation
- J Neurosci
- ISSN
- 0270-6474
- eISSN
- 1529-2401
- Publisher
- Society for Neuroscience
- Language
- English
- Date published
- 10/31/2012
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Iowa Neuroscience Institute; Craniofacial Anomalies Research Center
- Record Identifier
- 9984020770702771
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