Further pharmacological studies will be done to tease out the role of the AMY1 receptor in CGRP induced behaviors.
Finally, the increased squint in females but not male mice in response to amylin suggest that females may be more sensitive to amylin induced migraine-like behaviors. Additionally, amylin induced mechanical allodynia the plantar region of both female and male mice. Responses in male mice are not yet conclusive. Most notably, amylin and the AMY1 receptor are implicated in light-aversive behavior in female C57BL/6J mice. Squint behavior was only present in female mice.Ĭonclusion: Preliminary results suggest that amylin and the AMY1 receptor play a role in migraine-like behaviors in mice. For plantar von Frey, there was a decrease in threshold for with IP injections of amylin compared to its baseline. There was no difference between any treatment and vehicle for open field behavior in both male and female mice. However, in preliminary experiments, cotreatment with AC187 did not significantly affect the CGRP response in male mice. Amylin injection also induced migraine-like phenotypes in male mice. Furthermore, CGRP induced light aversion in females was partially rescued by co-injection of AC187. Results: In female mice, amylin treatment decreased the average time in light compared to vehicle. Finally, an automated squint test was used for the induction of spontaneous pain by amylin.
Tactile allodynia was measured using periorbital and plantar application of von Frey filaments. To control for anxiety, we also assessed the effects of amylin, CGRP, and AC187 in the open field assay. The average time in light was assessed for all treatments.
The use of the light aversion assay measures light sensitivity in mice, which we use as a surrogate for photophobia. Mice were tested 30-min after CGRP injection and immediately after amylin injection. Methods: Male and female C57BL/6J mice were injected IP with either vehicle, CGRP (0.1 mg/kg), amylin (0.5 mg/kg), or with a co-injection of both CGRP (0.1 mg/kg) and AC187 (1 mg/kg). Furthermore, we hypothesize that blocking the AMY1 receptor using the selective antagonist AC187 will inhibit these migraine-like behaviors. We hypothesize that the intraperitoneal (IP) injection of amylin will induce a migraine-like response in mice, including mechanical allodynia, facial grimace, and light-aversive behaviors. A critical question is whether or not amylin causes migraine-like symptoms and if CGRP binding to the AMY1 receptor contributes to CGRP-induced phenotypes.
Amylin and CGRP bind with equal affinity to the calcitonin receptor/RAMP1 complex (AMY1). Amylin is a member of the CGRP peptide family that shares a receptor with CGRP. One sentence summary: Like CGRP, amylin can induce migraine-like behaviors in mice suggesting a role for the amylin receptor in migraine.īackground: Calcitonin gene-related peptide (CGRP) is a neuropeptide that is necessary and sufficient for migraine in humans and can induce migraine-like symptoms in mice. 2ġ VA Center for the Prevention and Treatment of Visual Loss, Iowa City, IA, USA 2 University of Iowa, Iowa City, IA, USA CATEGORY: BASIC SCIENCE OR-01 Amylin induces migraine-like behaviors in mice
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