The effects of neonatal maternal deprivation and chronic unpredictable stresses on migraine-like behaviors in adult rats.

BACKGROUND: Stress is known to cause migraine. This study investigates the effects of neonatal maternal deprivation (MD) and chronic unpredictable stress (CUS) on migraine in rats. METHODS: Seventy rats were randomly divided into ten groups (five groups of each sex, and seven rats/group). The groups included: untreated intact, nitroglycerin (NTG) only, NTG + MD, NTG + CUS (10 weeks after birth), and NTG + MD + CUS. For the induction of MD, pups were separated from their mothers from postnatal day 2 to day 14. The CUS was conducted by daily exposure to different stressors for 2 weeks. For the induction of migraine after stress, NTG (5 mg/kg/IP) was administered every second day for 9 days. Afterward, NTG-related symptoms, including climbing behavior, facial rubbing, body grooming, freezing behavior, and head-scratching, were recorded for 90 min. Statistical differences between the groups were analyzed by one-way and two-way ANOVA followed by the Newman-Keuls test. RESULTS: Migraine symptoms, including increased head-scratching, facial rubbing, and decreased climbing behavior, were more significant in females than in males. Head scratching and facial rubbing increased in stressed females, but not in males as compared to NTG-treated rats. Body grooming was significantly decreased in MD males compared to the NTG group. The effects of NTG in MD + CUS on the rats did not differ from those in the MD or CUS groups. CONCLUSIONS: MD and CUS had a sex-related aggravating effect on the development of migraine, while the combination of MD and CUS had no additive migraine-aggravating effect.

The role of basolateral amygdala orexin 1 receptors on the modulation of pain and psychosocial deficits in nitroglycerin-induced migraine model in adult male rats.

BACKGROUND: Migraine headaches have been associated with sensory hyperactivity and anomalies in social/emotional responses. The main objective of this study was to evaluate the potential involvement of orexin 1 receptors (Orx1R) within the basolateral amygdala (BLA) in the modulation of pain and psychosocial dysfunction in a nitroglycerin (NTG)-induced rat model of migraine. METHODS: Adult male Wistar rats were injected with NTG (5 mg/kg, intraperitoneal) every second day over nine days to induce migraine. The experiments were done in the following six groups (6 rats per group): untreated control, NTG, NTG plus vehicle, and NTG groups that were post-treated with intra-BLA microinjection of Orx1R antagonist SB-334867 (10, 20, and 40 nM). Thermal hyperalgesia was assessed using the hot plate and tail-flick tests. Moreover, the elevated plus maze (EPM) and open field (OF) tests were used to assess anxiety-like behaviors. The animals' sociability was evaluated using the three-chamber social task. The NTG-induced photophobia was assessed using a light-dark box. RESULTS: We observed no change in NTG-induced thermal hyperalgesia following administration of SB-334867 (10, 20, and 40 nM). However, SB-334867 (20 and 40 nM) aggravated the NTG-induced anxiogenic responses in both the EPM and OF tasks. The NTG-induced social impairment was overpowered by SB-334867 at all doses. Time spent in the dark chamber of light-dark box was significantly increased in rats treated with SB-334867 (20 and 40 nM/rat). CONCLUSIONS: The findings suggest a role for Orx1R within the BLA in control comorbid affective complaints with migraine in rats.

Orexin one receptors within the basolateral amygdala are involved in the modulation of cognitive deficits associated with a migraine-like state in rats.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: Overall, the data provided an emerging role for the orexin system within BLA in the modulation of cognitive decline comorbid with migraine in rats.

Abscisic acid interplays with PPARγ receptors and ameliorates diabetes-induced cognitive deficits in rats.

OBJECTIVE: This study intended to evaluate if central administration of abscisic acid (ABA) alone or in combination with GW9662, a peroxisome proliferator-activated receptor γ (PPAR-γ) antagonist, could modulate learning and memory as well as hippocampal synaptic plasticity in a rat model of streptozotocin (STZ)-induced diabetes. MATERIALS AND METHODS: Intraperitoneal injection of STZ (65 mg/kg) was used to induce diabetes. Diabetic rats were than treated with intracerebroventricular (i.c.v.) administration of ABA (10, 15 and 20 µg/rat), GW9662 (3 µg/rat) or GW9662 (3 µg/rat) plus ABA (20 µg/rat). Animals' spatial and passive avoidance learning and memory performances were assessed by Morris water maze (MWM) and shuttle box tasks, respectively. Further, in vivo electrophysiological field recordings were assessed in the CA1 region. RESULTS: STZ diabetic rats showed diminished learning and memory in both MWM and shuttle box tasks. The STZ-induced memory deficits were attenuated by central infusion of ABA (10 and 20 µg/rat). Besides, STZ injection impaired long-term potentiation induction in CA1 neurons that was attenuated by ABA at 20 µg/rat. Central administration of GW9662 (3 µg/rat) alone did not modify STZ-induced spatial and passive avoidance learning and memory performances of rats. Further, GW9662 prevented ABA capacity to restore learning and memory in behavioral and electrophysiology trials. CONCLUSION: Altogether, ABA ameliorates cognitive deficits in rats via activation of PPAR-γ receptor in diabetic rats.

Physical exercise enhances vulnerability to migraine headache associated with CGRP up-expression in trigeminal nucleus caudalis of stressed rats.

OBJECTIVES: There is conflicting evidence on the effect of physical exercise on migraine development. Present study investigated the impact of treadmill exercise on migraine - associated symptoms and changes in calcitonin gene-related peptide (CGRP) expression in rats with and without maternal deprivation stress (MD). METHODS: Two days after birth, the male Wistar pups were randomly divided into four groups (n = 6) as follows: intact, exercise, MD, and MD plus exercise. The animals in the MD groups were separated from their dams 4 h per day for 2 weeks. At 8 weeks of age, the rats were exercised on a motor-driven treadmill for 4 weeks. Then, nitroglycerin (NTG) (5 mg/kg/IP) was used to induce migraine and pain-related symptoms were recorded for 90 min. NTG-related thermal hyperalgesia was measured by tail flick and hot plate methods. Finally, immunofluorescence staining of CGRP in trigeminal subnucleus caudalis (Vc) was performed. RESULTS: NTG - produced a significant headache symptoms and thermal hypersensitivity, which were aggravated following physical exercise in stressed or unstressed groups. Besides, NTG administration increased CGRP expression in the Vc of rats. Such effect was overpowered by treadmill running only in rats exposed to MD stress. CONCLUSION: These findings highlight the worsening effects of treadmill exercise for migraine in rats with and without MD stress. However, inflammatory response can further exacerbate in stressed rats.