بررسی نقش گیرنده های GABAA و GABAB در رفتارهای شبه اضطرابی ناشی از لیپوپلی ساکاریدها در آزمون جعبه تاریک و روشن در موش های سوری نر

نوع مقاله: مقاله پژوهشی

نویسندگان

1 گروه زیست شناسی، واحد تهران شمال، دانشگاه آزاد اسلامی، تهران، ایران

2 گروه زیست شناسی، واحد کرج، دانشگاه آزاد اسلامی، کرج، ایران

3 گروه میکروبیولوژی، واحد کرج، دانشگاه آزاد اسلامی، کرج، ایران

چکیده

سیستم گاباارژیک یک سیستم ضد اضطراب در مغز محسوب می­شود. بنابراین هدف از این مطالعه بررسی نقش گیرنده­های GABAA و GABAB در رفتارهای شبه اضطرابی ناشی از لیپوپلی ساکاریدها در موش­های سوری نر می­باشد. در این آزمایش موش­ها 2 ساعت بعد از تزریق  LPS موسیمول (05/0، 1/0 و 2/0 میکروگرم بر موش)، بیکوکولین (25/0، 5/0 و 1 میکروگرم بر موش)، باکلوفن (1، 2 و 4 میکروگرم  بر موش)، CGP (8/0, 4/0 , 2/ 0میکروگرم بر موش) و Celebrex را بصورت درون بطنی دریافت کردند. 5 دقیقه بعد از تزریق درون بطنی تست LDB انجام گرفت. این مطالعه نشان داد که موسیمول موجب کاهش معنی دار رفتار اضطرابی در آزمون LDB شد (05/0 > p < /em>). اما تجویز موسیمول و LPS تغییر معنی­داری نداشته است (P≥0.05). دوزهای مختلف بیکوکولین و LPS  موجب افزایش معنی­دار رفتار اضطرابی در  آزمون LDB شد (05/0 > p < /em>). باکلوفن وCGP به تنهایی و همراه با LPS تغییر معنی­داری در رفتار اضطرابی حیوان در  آزمون LDB نداشته است (05/0 > p < /em>). تزریق Celebrex متعاقب LPS موجب رفع رفتار شبه اضطرابی ناشی از تزریق LPS  شد. به طور کلی میتوان گفت رفتارهای شبه اضطرابی در حیوانات دریافت­کننده LPS ممکن است ناشی از مهار گیرنده­های GABAAو GABABو افزایش سطح فاکتورهای التهابی بافت مغز بوده باشد.

کلیدواژه‌ها


عنوان مقاله [English]

Evaluation the Role of GABAA and GABAB Receptors in Anxiety-like Behaviors Caused by Lipopolysaccharides in the Dark and Light Box (LDB) Test in Male Mice

نویسندگان [English]

  • Masoumeh Alishahi 1
  • Maryam Bananej 1
  • Jalal Solati 2
  • Ramin Hajikhani 1
  • Mostafa Ghaderic 3
1 Department of Biology, North Tehran Branch, Islamic Azad University, Tehran, Iran
2 Department of Biology, Islamic Azad University, Karaj Branch, Karaj, Iran
3 Department of Microbiology, Karaj Branch, Islamic Azad University, Karaj, Iran
چکیده [English]

Thegabaergic system is considered as the anti-anxiety system in the brain. The aim of this study was to investigate the role of GABAA and GABAB receptors in anxiety-like behaviors caused by lipopolysaccharides in male mice. In this test,mice were injected with lipopolysaccharide (LPS) (0.2 mg/kg), then injected with either muscimol (0.05, 0.1 or 0.2 µg/mouse), bicuculline (0.25, 0.5 or1 µg/mouse), baclofen (1, 2 or 4 µg/mouse) or CGP (0.2, 0.4 or 0.8 µg/mouse) 2 hours later and received intraventricular Celebrex. Five minutes after intraventricular injection, a dark and light box test was performed. The results of this study showed that musimol significantly reduced anxiety-like behavior in the LDB test (p < /em> < 0.05). The results of this study showed that musimol significantly reduced anxiety-like behavior in the LDB test (p < /em> < 0.05). However, the administration of musimol and LPS did not significantly change the animal’s anxiety-like behavior (p < /em> ≥ 0.05). Different doses of bioculin and LPS significantly increased the anxiety-like behavior in the LDB test (p < /em> < 0.05). Baclofen and CGP alone and with LPS did not significantly change the animal’s anxiety-like behavior on the LDB test (p < /em> ≥ 0.05). Celebrex injection after LPS relieved the anxiety-like behavior caused by LPS injection. In general, it can be claimed that anxiety-like behaviors in animals receiving LPS may be due to inhibition of GABAA and GABAB receptors and increase in the level of inflammatory factors in brain tissue.

کلیدواژه‌ها [English]

  • Lipopolysaccharide
  • Anxiety-like Behavior
  • GABAA
  • GABAB
  • Dark and Light Box
1-   Adriani W., Laviola G., 2000. A unique hormonal and behavioral hyporesponsivity to both forced novelty and d-amphetamine in periadolescent mice. Neuropharmacology, 39(2): 334-346.

2- Akhondzade S., Jafari S., Raisi F., Nasehi  A.A., Ghoreishi  A., Salehi  B., et al., 2009. Clinical trial of adjunctive celecoxib treatment in patients with major depression: a double blind and placebo controlled trial. Depression and Anxiety, 26(7): 607-611.

3- Barragan A., Weidner JM., Jin  Z., Korpi  E.R., Birnir  B., 2015. GABA ergic signalling in the immune system. Acta physiologica. Acta Physiol (Oxf), 213(4): 819-827.

4- Barbalho C.A., Nunes-de-Souza R.L., Canto-de-Souza A., 2009. Similar anxiolytic-likeeffects following intra-amygdala infusions of benzodiazepine receptor agonist and antagonist: evidence for the release of an endogenous benzodiazepine inverse agonist in mice exposed to elevated plus-maze test. Brain research, 1267: 65-76.

5. Bilkei-Gorzo A., Gyertyan I., Levay G., 1998.  mCPP-induced anxiety in the light-dark box in rats–a new method for screening anxiolytic activity. Psychopharmacology, 136(3): 291-298.

6.  Brustolim D., Ribeiro-dos-Santos R., Kast R., Altschuler E., Soares M.B.P., 2006. A new chapter opens in anti-inflammatory treatments: the antidepressant bupropion lowers production of tumor necrosis factor-alpha and interferon gamma in mice. International immunopharmacology. International Journal of Immunopharmacology, 6(6): 903-907.

7. Bowery  N., 2010. Historical perspective and emergence of the GABAB receptor. Advances in Pharmacology, 58: 1-18.

8. Cromer  BA, Morton  CJ, Parker ,  MW., 2002. Anxiety over GABAA receptor structure relieved by AChBP. Trends Biochem Sci.   27(6): 280-287.

9. Dalvi A., Rodgers RJ., 1996. GABAergic influences on plus-maze behaviourinmice. Psychopharmacology, 128(4): 380-397.

10. Dantzer R., O'Connor J.C., Freund G.G., Johnson R.W., Kelley K.W., 2008. From inflammation to
sickness and depression: when the immune system subjugates the brain. Nature Reviews and Neuroscience, 9(1):46

11. De Miranda A.S., Lacerda-Queiroz N., de Carvalho Vilela M., Rodrigues D.H, Rachid M.A., Quevedo J., et al., 2011. Anxiety-like behavior and proinflammatory cytokine levels in the brain of C57BL/6 mice infected with Plasmodium berghei (strain ANKA). Neuroscience Letters, 491(3): 202-6.

12. De Noronha S.R., Campos G.V., Abreu A.R., de Souza A.A., Chianca Jr D.A., de Menezes R.C., 2017. High fat diet induced-obesity facilitates anxiety-like behaviors due to GABAergic impairment within the dorsomedial hypothalamus in rats. Behavioral Brain Research, 316: 38-46.

13.       D'Mello C., Swain M.G., 2011. Liver-brain inflammation axis. American Journal of PhysiologyGastrointestinal and Liver Physiology, 301(5): G749-G61.

14.       Foster J.A., Neufeld K-A.M,. 2013. Gut–brain axis., how the microbiome influences anxiety and depression. Trends in Neuroscience, 36(5): 305-312

15.  Ge Li., Liu L., Liu H., Liu S., Xue  H., Wang X., 2015. Resveratrol abrogates lipopoly saccharide-induced depressive-like behavior, neuroinflammatory response, and CREB/BDNF signaling in mice. European Journal of Pharmacology, 5(768): 49-57.

16. Heldt S., Mou L., Ressler K., 2012. In vivo knockdown of GAD67 in the amygdala disrupts fear extinction and the anxiolytic-like effect of diazepam in mice. Translational Psychiatry, 2(11): e181.

17. Jangra A.,  Lukhi M.M., Sulakhiya K, Baruah C.C., Lahkar M. 2014. Protective effect of mangiferin against lipopolysaccharide-induced depressive and anxiety-like behaviour in mice.
European Journal of Pharmacology,  740: 337-345.

18. Jiang H., Wang Z., Wang Y., Xie K., Zhang Q., Luan Q., et al., 2013. Antidepressant-like effects of curcumin in chronic mild stress of rats: involvement of its anti-inflammatory action. Progress Neuro Psychopharmacology and Biological Psychiatry, 47:33-39.

19. Jin Z., Mendu S.K., Birnir  B., 2013. GABA is an effective immunomodulatory molecule. Amino acids, 45(1): 87-94.

20. Knapp D.J., Overstreet D.H., Breese   GR,. 2007.  Baclofen blocks expression and sensitization of anxiety‐like behavior in an animal model of repeated stress and ethanol withdrawal. Alcoholism Clinical and Experimental Research, 31(4):582-595

21. Krogh J., Benros ME., Jørgensen MB., Vesterager L., Elfving B., 2014. Nordentoft M. The association between depressive symptoms, cognitive function, and inflammation in major depression. Brain Behavior Immunology, 35: 70-76

22. Lacosta S., Merali Z., Anisman H. , 1999. Behavioral and neurochemical consequences of lipopolysaccharide in mice: anxiogenic-like effects. Brain Research, 818(2): 291-303

23. Mello B.S.F., Monte A.S., McIntyre R.S., Soczynska J.K., Custódio C.S., Cordeiro R.C., 2013.  Effects of doxycycline on depressive-like behavior in mice after lipopolysaccharide (LPS) administration. Psychiatric Research, 47(10): 1521-1529.

24. Mihic S., Sanna E., Whiting P., Harris R., 1995. Pharmacology of recombinant GABAA receptors. Advances in Biochemical Psychopharmacology, 48:17

25.  Mombereau C., Kaupmann K., Gassmann  M., Bettler B, van der Putten H., Cryan J.F., 2005. Altered anxiety and depression-related behaviour in mice lacking GABAB (2) receptor subunits. Neuroreport, 28;16(3): 307-310.

26. Mody I., Pearce R.A,. 2004. Diversity of inhibitory neurotransmission through GABAA receptors. Trends in Neurosciences, 27(9): 569-575.

27.   Nascimento , J.O.G., Zangrossi Jr. .H., Viana , M.d.B., 2010.  Effects of reversible inactivation of the dorsomedial hypothalamus on panic-and anxiety-related responses in rats. Brazilian Journal of Medical and Biological Research, 43(9): 869-873

28. Nunes-de-Souza R., Canto-de-Souza A., Da-Costa M., Fornari R., Graeff  F., Pela I., 2000. Anxietyinduced antinociception in mice: effects of systemic and intra-amygdala administration of
8-OH-DPAT and Midazolam. Psychopharmacology
, 150(3): 300-310.

29. Park B.S., Lee J.O., 2013. Recognition of lipopolysaccharide pattern by TLR4 complexes. Experimental and Molecular Medicine, 45(12): e66.

30. Pesold C., Treit D., 1995. The central and basolateral amygdala differentially mediate the anxiolytic effects of benzodiazepines. Brain Research, 13;671(2): 213-221.

31. Salazar A., Gonzalez-Rivera B.L., Redus L., Parrott J.M., O'connor J.C. 2012. Indoleamine 2, 3-dioxygenase mediates anhedonia and anxiety-like behaviors caused by peripheral lipopolysaccharide immune challenge. Hormones and Behavior, 62(3): 202-209.

32. Shekhar A., Hingtgen J., DiMicco J. , 1990. GABA receptors in the posterior hypothalamus regulate experimental anxiety in rats. Brain Research, 512(1): 81-88.

33. Sieghart W., 2006. Structure, pharmacology, and function of GABAA receptor subtypes. Advances in Pharmacology, 54: 231-263.

34. Soncini R., de Souza D.F., 2012. Neves A.P., Braga D.S., Andrade C.A., Giusti-Paiva A.Dipyrone attenuates acute sickness response to lipopolysaccharide in mice. Neuroscience Letters, 516(1): 114-118.

35. Sulakhiya K., Keshavlal G.P., Bezbaruah B.B., Dwivedi S., Gurjar S.S., Munde N., et al., 2016. Lipopolysaccharide induced anxiety-and depressive-like behaviour in mice are prevented by chronic pre-treatment of esculetin. Neuroscience Letters, 611: 106-111.

36. Sulakhiya K., Kumar P., Jangra A., Dwivedi S., Hazarika N.K., Baruah C.C., et al,. 2014. Honokiol abrogate lipopolysaccharide-induced depressive like behavior by impedingneuro in flammation and oxido-nitrosative stress in mice. European Journal of Pharmacology, 744: 124-131.

38. Zaretskaia M.V., Zaretsky D.V., Sarkar S., Shekhar A., DiMicco J.A., 2008. Induction of Fos-immunoreactivity in the rat brain following disinhibition of the dorsomedial hypothalamus. Brain Research, 200: 39-50.