بررسی اثر ریسپریدون بر القاء وابستگی روانی و تعداد نورون های هیپوکامپ در موش های صحرایی نر بالغ

محورهای موضوعی : فصلنامه زیست شناسی جانوری

زهرا منصوری آرانی ¹ , نسرین حیدریه ² , حمیدرضا بنفشه ³ , غلامرضا قوی پنجه ⁴ , مجید لطفی نیا ⁵

1 - گروه زیست شناسی، واحد قم، دانشگاه آزاد اسلامی، قم، ایران
2 - گروه زیست شناسی، واحد قم، دانشگاه آزاد اسلامی، قم، ایران
3 - گروه فارماکولوژی، دانشکده پزشکی، دانشگاه علوم پزشکی کاشان، کاشان، ایران
4 - گروه فارماکولوژی، دانشکده پزشکی، دانشگاه علوم پزشکی کاشان، کاشان، ایران
5 - گروه بیوتکنولوژی مرکز تحقیقات فیزیولوژی پژوهشکده علوم پایه دانشگاه علوم پزشکی کاشان، کاشان، ایران

تاریخ دریافت : 1401/06/23 تاریخ پذیرش : 1401/10/18 تاریخ انتشار : 1402/06/01

کلید واژه: هیپوکامپ, ریسپریدون, وابستگی روانی, نورون,

چکیده مقاله :

وابستگی روانی به مواد، تمایل به مصرف ماده یا چیزی که دارای اثرات لذت بخش بوده و تولید رضایت کند، می باشد مواد مختلفی باعث ایجاد این وابستگی می شوند. مطالعات قبلی تأثیر احتمالی ریسپریدون را بر سیستم پاداش مغزی و درگیری گیرنده‌های مختلف در ترجیح مکان شرطی شده (CPP) نشان می‌دهد. بنابراین مطالعه حاضر با هدف بررسی اثر ریسپریدون بر القاء وابستگی روانی و تعداد نورون های هیپوکامپ طراحی شد. برای این پژوهش از 40 موش صحرایی نر نژاد ویستار با محدوده وزنی230-280 گرم استفاده شد. تزریق داخل صفاقی ریسپریدون با دوزهای 1، 2 و 4 میلی گرم/کیلوگرم انجام شد. در پایان آزمایشات هیپوکامپ حیوانات خارج و توسط فرمالین تثبیت و سپس برشگیری شده و پس از رنگ آمیزی، برای ارزیابی بافت شناسی و شمارش نورونی مورد استفاده قرار گرفتند. نتایج این مطالعه نشان داد که تجویز ریسپریدون با دوز 2 و 4 میلی گرم/کیلوگرم موجب افزایش معنی دار CPP می گردد (05/0 > p). همچنین در ارزیابی بافت شناسی، در همه گروه های ریسپریدون (1، 2 و 4 میلی گرم/کیلوگرم) تخریب نورونی مشاهده نشد. با توجه به نتایج بدست آمده می توان نتیجه گرفت که ریسپریدون در دوزهای بالاتر ایجاد باعث افزایش ترجیح مکان شرطی و یادگیری و وابستگی می شود و در درمان مورد توجه قرار گیرد.

چکیده انگلیسی:

Psychological dependence on substances is the desire to consume substances or something that has pleasurable effects and produces satisfaction. Various substances cause this dependence. Previous studies indicate the possible effect of risperidone on the brain reward system and the involvement of different receptors in conditioned place preference (CPP). Therefore, the present study was designed with the aim of investigating the effect of risperidone on the induction of psychological dependence and the number of hippocampal neurons. For this study, 40 male Wistar rats with a weight range of 230-280 grams were used. Risperidone was injected intraperitoneally with doses of 1, 2 and 4 mg/kg. At the end of the hippocampus experiments, the animals were taken out and fixed by formalin, then cut and after staining, they were used for histological evaluation and neuronal counting. The results of this study showed that the administration of risperidone with a dose of 2 and 4 mg/kg causes a significant increase in CPP (p < 0.05). Also, in histological evaluation, no neuronal destruction was observed in all risperidone groups (1, 2 and 4 mg/kg). According to the obtained results, it can be concluded that risperidone in higher doses causes an increase in conditioned place preference and learning and dependence and should be considered in treatment.

منابع و مأخذ:

1. Abbasi Maleki S,Nouri M, Eskandary H, Abbasi Maleki N, Cheraghyan S. 2011. The effect of peripheral and intracerebroventricular injection of vitamin B6 on the positive reinforcing effect of morphine in the conditioned place preference (CPP) model in male rats. Journal of Tabriz University of Medical Sciences, 33(5):85-90.


2. Ahmadian S.M., Alaei H., Ghahremani P. 2019. An Assessment between D1 receptor agonist and D2 receptor antagonist into the ventral tegmental area on conditioned place preference and locomotor activity. Advanced Biomedical Research, 8:72.


3. Bardgett M.E., Downnen T., Crane C., Baltes Thompson E.C., Muncie B., Steffen S.A., Yates J.R., Pauly J.R. 2020. Chronic risperidone administration leads to greater amphetamine-induced conditioned place preference. Neuropharmacology, 179:108276.


4. Boman L, De Butte M. 2019. Neurobehavioral effects of chronic low-dose risperidone administration in juvenile male rats. Behavioural Brain Research, 363:155-160.


5. BruntonL., Chabner B., Knollman B. 2014. Goodman and Gilman's The Pharmacological Basis of Therapeutics, 12th Edition, McGraw-Hill Education, 2109 p.


6. Chen S., Lian J., Su Y., Deng C. 2022. Effects of Risperidone and Prenatal Poly I:C Exposure on GABA_A Receptors and AKT-GSK3β Pathway in the Ventral Tegmental Area of Female Juvenile Rats. Biomolecules, 12(5):732.


7. Choi Y.K., Moran-Gates T., Gardner M.P., Tarazi F.I. 2010. Effects of repeated risperidone exposure on serotonin receptor subtypes in developing rats. European Neuropsychopharmacology, 20:187-194.


8. Elahi-Mahani A., Heysieattalab S., Hosseinmardi N., Janahmadi M., Seyedaghamiri F., Khoshbouei 2018. Glial cells modulate hippocampal synaptic plasticity in morphine dependent rats. Brain Research Bulletin, 97:106-140.


9. Favaroni Mendes L.A., Menescal-de-Oliveira L. 2008. Role of cholinergic opiodergic and GABAergic neurotransmission of the dorsal hippocampus in the modulation of nociception in guinea pigs. Life Science, 83: 644-650.


10. Floresco S.B., Magyar O., Ghods-Sharifi S., 2006. Multiple Dopamine receptor subtypes in the medial prefrontal cortex of the Rat regulate set-shifting. Neuropsychopharmaco logy, 31:297-309.


11. Hadizadeh Assar S., Hosseini Sharifabad M., Yadegari M. 2019. Effects of methamphetamine toxicity on the nervous system.ShafayeKhatam, 6)3):91-99.


12. Horacek J., Bubenikova-Valesova V., Kopecek M., Palenicek T., Dockery C., Mohr P., Höschl C. Bubenikova-Valesova V., Kopecek M, Palenicek T., Dockery C., Mohr P., Höschl C. Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. CNS Drugs, 20(5):389-409.


13. Hyman S.E., Malenka R.C. 2001. Addiction and the brain: the neurobiology of compulsion and its persistence Nature Reviews, Neuroscience, 2(10):695-703.


14. Jafari F., Hemmati S، Fadai F، Dolatshahi B. Comparing the effects of risperidone and haloperidol on the general symptoms of schizophrenia. Rehabilitation Archive (Rehabilitation), 8(29):9-13.


15. Jenkins T.A., Elliott J.J., Ardis T.C., Cahir M., Reynolds G.P., Bell R., Cooper S.J. Cooper Tryptophan depletion impairs object-recognition memory in the rat: Reversal by risperidone. Behavioural Brain Research,  208(2):479-483


16. Kajero J., Seedat S., Ohaeri J., Akindele A., Aina O. 2022. The effects of cannabidiol on behavioural and oxidative stress parameters induced by prolonged haloperidol administration. Acta Neuropsychiatrica, 2022:1-11.


17. Katebi  , Haghparast  A,. 2018. Involvement of D1- and D2-like dopamine receptors in the dentate gyrus in the acquisition, expression, and extinction of the morphine-induced conditioned place preference in rats. Behavioural Brain Research, 353(2018):185-193.


18. Keller İ. Eriman, H. Erdinc, M. Uyar E. 2022. Risperidone and ethyl pyruvate have protective effects against ketamine-induced cognitive impairments in mice. European Review for Medical and Pharmacological Sciences, 26:1708-1716.


19. Koller E.A., Cross J.T., Doraiswamy P.M., Malozowski S.N. 2003. Pancreatitis associated with atypical antipsychotics: from the food and drug administration's MedWatch surveillance system and published reports. Pharmacotherapy, 23(9):1123-1130.


20. Liang J., Ping X.J., Li Y.J., Ma Y.Y., Wu L.Z., Han J.S. 2010. Morphine-induced conditioned place preference in rats is inhibited by electroacupuncture at 2 Hz: role of enkephalin in the nucleus accumbens. Neuropharmacology, 58(1):233-2


21. Line K., Massucci J.L., Marion D.W., Dixon C.E. 2002. Attenution of working memory and spatialacquisition deficits after a delayed and chronic bromocriptine treatment regiune in rats subjected of traumatic brain injury by controlled cortical impact. Journal of Neurotroma, 19(4):415-425.


22. Marighetto A., Valerio S., Philippin J.N., Bertaina-Anglade V., Drieu la Rochelle C., Jaffard R., Morain P. 2008. Comparative effects of the dopaminergic agonists piribedil and bromocriptine in three different memory paradigms in rodents. Journal of Psychopharmacology, 22(5):511-521.


23. McIntosh A.L., Ballard T.M., Steward L.J., Moran P.M., Fone K.C. The atypical antipsychotic risperidone reverses the recognition memory deficits induced by post-weaning social isolation in rats. Psychopharmacology, 228(1):31-42.


24. Moaddab M., Haghparast A., Hassanpour-Ezatti M. 2009. Effects of reversible inactivation of the ventral tegmental area on the acquisition and expression of morphine-induced conditioned place preference in the rat. Behavioral Brain Research, 198(2):466-471.


25. Mobasher M., Sahraei H., Sadeghi-Rad B., Kamalinejad M., Shams J. 2006. The effects of Crocus sativus extract on the acquisition and expression of morphine-induced conditioned place preference in mice. ournal of Rafsanjan University of Medical Sciences, 5(3):143-150.


26. Mojabi N.S., Eidi A., Kamalinejad M., Khamseh F., Khoshbaten A., Noroozzadeh A., Zighymat F., Sahraei H. 2008. The effects of intra-nucleus accumbens shell injections of alcohlic extract of Crocus sativus on the acquisition and expression of morphine-induced conditioned place preference in rats. Physiology and Pharmacology, 12(2):121-128.


27. Pandina G.J., Bossie C.A., Youssef E., Zhu Y., Dunbar F. 2007. Risperidone Improves Behavioral Symptoms in Children with Autism in a Randomized, Double-Blind, Placebo-Controlled Trial. Journal of Autism and Developmantal Disorders, 37(2):367-373.


28. Rouge-Pont F., Usiello A., Benoit-Marand M., Gonon F., Piazza P.V., Borrelli E. 2002. Changes in extracellular dopamine induced by morphine and cocaine: crucial control by D2 receptors. Journal of Neuroscience, 22(8):3293-3301.


29. Samuels E.R, Szabadi E. 2008. Functional neuroanatomy of the noradrenergic locus coeruleus: Its roles in the regulation of arousal and autonomic function part II: physiological and pharmacological manipulations and pathological alterations of locus coeruleus activity in humans. Current Neuropharmacology, 6(3):254-285.


30. Taghavi Rafsanjani A., Haeri Rohani A., Pourshanazari A., Shamsizadeh A., Allahtavakoli M. 2013. Effect of nicotine administration on physical and psychological signs of withdrawal syndrome induced by single or repeated doses of morphine in rat. Journal of Sabzevar University of Medical Sciences, 20(3(:347-358.


31. Tale F., Ghaderi Pakdel F., Shahabi P., Naderi S. 2016. Burst firing of the ventral Ttegmental area neurons through bicuculline-induced GABA-A receptor blockade. ShafayeKhatam, 4(2):33-46.


32. Tavakoli F., Hoseini S., Mokhtari M., Vahdati A. 2014. Effect of memory attenuation and light music on morphine dependency in male mature mice using conditioned place preference. Feyz,18(1):1-8. [in Persian]


33. Tendilla-Beltrán H., Meneses-Prado S., Vázquez-Roque R.A., Tapia-Rodríguez M., Vázquez-Hernández A.J., Coatl-Cuaya H., Martín-Hernández D., MacDowell K.S., Garcés-Ramírez L., Leza J.C., Flores G., Risperidone ameliorates prefrontal cortex neural atrophy and oxidative/nitrosative stress in brain and peripheral blood of rats with neonatal ventral h lesion. Journal of Neuroscience, 39(43):8584–8599.


34. Varadinova M., Bogdanov G., Markova 2019. Effects of risperidone on Learning and memory arameters in experimental model of autism. Trakia Journal of Sciences, 3:203-207.


35. Yu W., Zhu M., Fang H., Zhou J., Ye L., Bian W., Wang Y., Zhu H., Xiao J., Zhu H. Li H. 2019. Risperidone Reverses the Downregulation of BDNF in Hippocampal Neurons and MK801-Induced Cognitive Impairment in Rats. Frontiers in Behavioral Neuroscience, 13:163.


36. Zarrindast R., Faraji N., Rostami P., Sahraei H., Ghoshouni H. 2003. Cross-tolerance between morphine- and nicotine-induced conditioned place preference in mice. Pharmacology, Biochemistry and Behavior, 74:363-369.