sb-334867-a and Migraine-Disorders

Orexin 1 receptors (Orx1R) and cannabinoid 1 receptors (CB1R) are implicated in migraine pathophysiology. This study evaluated the potential involvement of Orx1R and CB1R within the ventrolateral periaqueductal gray matter (vlPAG) in the modulation of anxiety-like behavior and social interaction of migraineurs rats. A rat model of migraine induced by recurrent administration of nitroglycerin (NTG) (5 mg/kg/i.p.). The groups of rats (n = 6) were then subjected to intra-vlPAG microinjection of orexin-A (25, 50 pM), and Orx1R antagonist SB334867 (20, 40 nM) or AM 251 (2, 4 μg) as a CB1R antagonist. Behavioral responses were evaluated in elevated plus maze (EPM), open field (OF) and three-chambered social test apparatus. NTG produced a marked anxiety like behaviors, in both EPM and OF tasks. It did also decrease social performance. NTG-related anxiety and social conflicts were attenuated by orexin-A (25, 50 pM). However, NTG effects were exacerbated by SB334867 (40 nM) and AM251 (2, 4 μg). The orexin-A-mediated suppression of NTG-induced anxiety and social conflicts were prevented by either SB334867 (20 nM) or AM251 (2 μg). The findings suggest roles for Orx1R and CB1R signaling within vlPAG in the modulation of migraine-induced anxiety-like behavior and social dysfunction in rats.

Topics: Animals; Anxiety; Behavior, Animal; Benzoxazoles; Male; Migraine Disorders; Naphthyridines; Orexin Receptors; Periaqueductal Gray; Piperidines; Pyrazoles; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Receptors, Neuropeptide; Social Behavior; Urea

This study explored the possible role of orexin one receptors (Orx1R) in the basolateral amygdala (BLA) on the modulation of nitroglycerin (NTG)-induced migraine-like symptoms. In addition, pain-induced subsequent alteration in learning and memory competence was evaluated in the adult male Wistar rats.. The rats were given NTG (5 mg/kg, i.p.) every two days (for nine-day) to induce a migraine-like state. The migraine animals were treated with intra-BLA infusion of an Orx1R antagonist SB 334,867 (10, 20, and 40 nM/rat) or its vehicle DMSO. The NTG-induced migraine symptoms were recorded for 90 min. Spatial and passive avoidance performances were assessed by Morris water maze (MWM) and shuttle box tasks, respectively.. In comparison with control, NTG produced significant migraine-like symptoms characterized by a decrease in cage climbing and an increase in head-scratching, freezing, and facial grooming behavior. Intra-BLA infusion of SB 334,867 (40 nM/rat) significantly decreased cage climbing and increased facial grooming responses in NTG-treated rats. Moreover, all administrated doses of SB 334,867 increased NTG-evoked head-scratching and freezing behavior. Besides, NTG impaired learning and memory performances in both tests, which were exaggerated by post-injection of SB 334,867 (40 nM/rat).. Overall, the data provided an emerging

Topics: Animals; Basolateral Nuclear Complex; Benzoxazoles; Cognitive Dysfunction; Male; Migraine Disorders; Naphthyridines; Orexin Receptor Antagonists; Orexin Receptors; Rats; Rats, Wistar; Urea

This study aims to explore whether orexin 1 receptors (Orx1R) in the ventrolateral periaqueductal gray matter (vlPAG) play a role in the modulation of migraine headaches in adult male Wistar rats. To model chronic migraine-associated pain, nitroglycerin (NTG) (5 mg/kg/IP) was administered to test subjects every second day for 9 days. After the last NTG injection, rats were randomly separated into the following groups (n = 6): orexin-A (OrxA) groups that received intra-vlPAG OrxA (25, 50, and 100 pM), an Orx1R antagonist group, a SB-334867 (20 μM) group; and a SB-334867 (20 μM) + OrxA (100 pM) group. After 10 min, migraine-associated behavioral symptoms were recorded in all animals for up to 90 min. Light-dark chamber and hot plate tests were used for assessing light aversion and thermal hyperalgesia, respectively. Calcitonin gene-related peptide (CGRP)-positive cells were detected in the trigeminal nucleus caudalis (Vc) by immunofluorescence microscopy. NTG caused significant freezing behavior, which was prevented by all OrxA doses. Moreover, OrxA (100 pM) could obstruct NTG-induced increases in facial rubbing and decreases in climbing and body grooming. Furthermore, NTG-induced light aversion and thermal hyperalgesia were attenuated by OrxA at doses of 50 and 100 pM. The effects of OrxA were significantly blocked by SB-334867 (20 μM). Besides, OrxA (100 pM) decreased NTG-induced CGRP upregulation. The data revealed that the activation of Orx1Rs in the vlPAG is effective in relieving NTG-induced migraine symptoms mainly by the downregulation of CGRP in the Vc of rats.

Topics: Animals; Benzoxazoles; Calcitonin Gene-Related Peptide; Male; Microinjections; Migraine Disorders; Naphthyridines; Nitroglycerin; Orexin Receptor Antagonists; Orexin Receptors; Periaqueductal Gray; Rats; Rats, Wistar; Trigeminal Nuclei; Up-Regulation; Urea