Clinically relevant behavioral endpoints in a recurrent nitroglycerin migraine model in rats.
BACKGROUND
This research sought to further validate the rat nitroglycerin (NTG) migraine model by comparing the effects of single versus recurrent NTG episodes on behavioral endpoints that mirror ICHD-3 diagnostic criteria for migraine, and to determine if the altered behavioral endpoints are reduced after administration of sumatriptan.


METHODS
Separate cohorts of rats were administered NTG (10 mg/kg/2 ml) or saline (Experiment 1: single injection; Experiment 2: repeated injections; Experiment 3: repeated injections with sumatriptan [0.0, 0.3 and 1.0 mg/kg/ml] rescue. Behavioral endpoints were assessed 2 h after final NTG administration and included time in light/dark chambers for photophobia and activity, pain facial ratings, and cool (5 °C) and warm (46 °C) tail dip.


RESULTS
The first two experiments demonstrated that repeated (n = 5) but not single NTG injections produced photophobia, decreased activity, and yielded less weight gain than saline injections. Experiment 3 showed that sumatriptan attenuated hypoactivity, reduced facial expressions of pain, and reversed weight alterations in a dose-dependent manner.


CONCLUSIONS
These findings identify numerous clinical homologies of a recurrent NTG rat migraine model that may be useful for screening novel pharmacotherapies.
Department of Psychology, University of Mississippi, Oxford, MS, 38677, USA. pysufka@olemiss.edu.|Research Institute of the Pharmaceutical Sciences, University of Mississippi, Oxford, MS, 38677, USA. pysufka@olemiss.edu.|Department of Pharmacology, University of Mississippi, Oxford, MS, 38677, USA. pysufka@olemiss.edu.
Kenneth J
KJ
Sufka
Department of Psychology, University of Mississippi, Oxford, MS, 38677, USA.
Stephanie M
SM
Staszko
Department of Psychology, University of Mississippi, Oxford, MS, 38677, USA.
Ainslee P
AP
Johnson
Department of Psychology, University of Mississippi, Oxford, MS, 38677, USA.
Morgan E
ME
Davis
Department of Psychology, University of Mississippi, Oxford, MS, 38677, USA.
Rachel E
RE
Davis
Department of Psychology, University of Mississippi, Oxford, MS, 38677, USA.
Todd A
TA
Smitherman
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D008297:Male; D008881:Migraine Disorders / Q000139:chemically induced / Q000175:diagnosis* / Q000188:drug therapy; D009043:Motor Activity / Q000187:drug effects*; D005996:Nitroglycerin; D020795:Photophobia / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy; D051381:Rats; D058825:Serotonin 5-HT1 Receptor Agonists / Q000494:pharmacology / Q000627:therapeutic use; D018170:Sumatriptan / Q000494:pharmacology / Q000627:therapeutic use; D016896:Treatment Outcome; D014665:Vasodilator Agents
D058825:Serotonin 5-HT1 Receptor Agonists; D014665:Vasodilator Agents; D018170:Sumatriptan; D005996:Nitroglycerin
Animal models; Headache; Migraine; Nitroglycerin; Translational research