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  1. Fulltext Histopathological effects of repeated 14-day administration of rizatriptan benzoate in a nitroglycerin-induced migraine rabbits model
    Al-Saadi R, Mohammed Jawad ZJ, Khalaf OH, Muhsain SNF
    Open Vet J, 2025 Jan;15(1):179-186.
    PMID: 40092178 DOI: 10.5455/OVJ.2024.v15.i1.17
    BACKGROUND: Migraine is one of multiple attack neurological conditions that causes moderate to severe headaches with no defined pathophysiology and few animal models.

    AIM: Establishing an animal model that reproduces migraine-like action is important in medical research to identify the mechanism underlying this disorder. Additionally, it facilitates the availability and reliability of new models that may act as human surrogate models.

    METHOD: Rabbits were divided into four groups. Negative group, migraine group, rizatriptan-nitroglycerin group, and rizatriptan group. The frequency of head scratching and the histopathological changes in the brain, liver, kidney, and heart for groups were evaluated in all groups.

    RESULTS: The behavioral characteristic of head scratching was significantly increased in the NTG group (50.4 ± 3.8) compared with the control group (9.2 ± 1.3) after 30 min of the experiment. Moreover, animals treated with rizatriptan benzoate (Riza) 10 mg/kg/orally for 14 days followed by NTG injection showed a significant decrease in the head scratch action (16.8 ± 2.3 and 17.6 ± 3.3) than the animals of NTG group (50.4 ± 3.8 and 43.6 ± 2.3) after 30 min and 60 min, respectively. Furthermore, animals treated with Riza alone showed no statistical differences in the head scratches (7.8 ± 1.3, 9.2 ± 0.8, 10.6 ± 1.1 and 9.6 ± 1.3, respectively) during the 120 min of the experiment, compared with the control group. Histopathological alterations in the brain of rabbits that received NTG showed severe diffuse dilated and engorged blood vessels. These changes were also recorded in the liver and kidney of this group. This marked vasodilation of blood vessels and central and portal veins confirms the successful induction of migraine in the rabbit model. In contrast, animals treated with Riza for 14 days demonstrated substantially less vascular dilation following NTG injection. No significant pathological lesions were observed in animals treated with Riza.

    CONCLUSION: The current study successfully established a rabbit model of migraine using a single dose of NTG to induce migraine-like behavior. Moreover, pre-treatment with rizatriptan benzoate for fourteen days significantly reduced the symptoms of migraine and histopathological changes in different organs.

    Matched MeSH terms: Serotonin Receptor Agonists/pharmacology
  2. Serotonergic treatment normalizes midbrain dopaminergic neuron increase after periaqueductal gray stimulation
    Tan SZK, Temel Y, Chan AY, Mok ATC, Perucho JAU, Blokland A, et al.
    Brain Struct Funct, 2020 Sep;225(7):1957-1966.
    PMID: 32594260 DOI: 10.1007/s00429-020-02102-w
    Electrical stimulation of the dorsolateral periaqueductal gray (dlPAG) in rats has been shown to elicit panic-like behaviour and can be a useful as an unconditioned stimulus for modelling anticipatory fear and agoraphobia in a contextual fear conditioning paradigm. In this study, we further analysed our previous data on the effects of escitalopram (a selective serotonin reuptake inhibitor, SSRI) and buspirone (a 5-HT1A receptor partial agonist) on dlPAG-induced anticipatory fear behaviour in a rat model using freezing as a measure. We then attempted to unravel some of the interactions with dopamine signalling using tyrosine hydroxylase (TH) immunohistochemistry to probe the effects on dopaminergic neurons. We showed that acute treatment of escitalopram, but not buspirone, was effective in reducing anticipatory freezing behaviour, while chronic administrations of both drugs were effective. We found that the dlPAG stimulation induced increase number of dopaminergic neurons in the ventral tegmental area (VTA) which was reversed in both chronic buspirone and escitalopram groups. We further found a strong positive correlation between the number of dopaminergic neurons and freezing in the VTA and showed positive correlations between dopaminergic neurons in the VTA and substantia nigra pars compacta (SNpc) in escitalopram and buspirone groups, respectively. Overall, we showed that chronic treatment with an SSRI and a 5-HT1A agonist reduced anticipatory freezing behaviour which seems to be associated, through correlative studies, with a reversal of dlPAG stimulation induced increase in number of dopaminergic neurons in the VTA and/or SNpc.
    Matched MeSH terms: Serotonin Receptor Agonists/pharmacology*
  3. Fulltext Involvement of monoaminergic system in the antidepressant-like effect of aqueous extract of Channa striatus in mice
    Saleem AM, Taufik Hidayat M, Jais AM, Fakurazi S, Moklas MA, Sulaiman MR, et al.
    Eur Rev Med Pharmacol Sci, 2013;17(15):2019-22.
    PMID: 23884821
    BACKGROUND: In our previous study, the aqueous extract of Channa striatus (family: Channidae) fillet (AECSF) showed an antidepressant-like effect in mice. However, the mechanism of the antidepressant-like effect is unknown.
    AIM: The objective of this study was to explore the involvement of monoamines in the antidepressant-like effect of AECSF in mice.
    MATERIALS AND METHODS: AECSF was prepared by steaming the fillets of C. striatus. The male ICR mice were pretreated with various monoaminergic antagonists viz., p-chlorophenylalanine (100 mg/kg, i.p.), prazosin (1 mg/kg, i.p.) and yohimbine (1 mg/kg, i.p.), SCH23390 (0.05 mg/kg, s.c.) and sulpiride (50 mg/kg, i.p.) followed by treatment with AECSF and tested in tail suspension test (TST). Two-way ANOVA with Tukey test were used at p < 0.05 for significance.
    RESULTS: The pretreatments with p-chlorophenylalanine, prazosin and yohimbine, but not with SCH23390 and sulpiride, were able to reverse the antidepressant-like effect of AECSF in TST.
    CONCLUSIONS: The antidepressant-like effect of AECSF may be mediated through the serotonergic and noradrenergic systems and not through the dopaminergic system.
    Matched MeSH terms: Serotonin Receptor Agonists/pharmacology*
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