Survey on the interaction effect of low doses of ketamine on morphine-induced polycystic ovary syndrome in rat

Document Type : Original Article

Authors

1 Department of Biology, Faculty of Basic Sciences, Shahed University, Tehran, Iran

2 Department of Pathology, Faculty of Medicine, Shahed University, Tehran, Iran

Abstract

Background and Objective: Morphine can induce PCOS (Polycystic ovary syndrome) probably by changing glutamate level at the hypothalamic nuclei. This study used low doses of ketamine to survey the interaction of ketamine with morphine-induced PCOS.
Materials and Methods: 48 female Wistar rats were selected as virgins in the weight range of 220-250 g, and categorized randomly into eight groups. The first group received morphine (5 mg/kg) intraperitoneally. The second to fourth groups received ketamine (1, 2, and 4 mg/kg). In groups 5 to 7, the ketamine (1, 2, and 4 mg/kg) was pre-injected to morphine (5 mg/kg) over a period of 20 min. Control group received only saline (1 ml/kg). After 48 h, the blood and serum specimens were provided to record hormone levels, and the animals’ ovaries and uteri were biometrically examined and stained by H & E. Statistical analysis was performed by analysis of variance (ANOVA) under α=0.05.
Results: The morphine as well as single ketamine induced the PCOS. However, taking ketamine prior to morphine caused a meaningful reduction in the number of cysts in the ovary. There was also a relative increase in uterine diameter in the group receiving morphine, which was stopped due to ketamine pre-treatment. These effects showed correlation with decreased levels of FSH, and change in estrogen, and prolactin amounts.
Conclusion: The interference effect of ketamine with morphine is completely dependent on changes in gonadotropin level.

Keywords

References

  1. Diamanti-Kandarakis E, Kouli CR,  Bergiele AT, Filandra FA, Tsianateli  TC, Spina GG, et al. A survey of the polycystic ovary syndrome in the Greek island of Lesbons: hormonal and metabolic profile. Journal of Clinical Endocrinology and Metabolism 1999; 84:4006-11.
  2. Dabadghao P. Polycystic ovary syndrome in adolescents. Best Practice & Research Clinical Endocrinology & Metabolism 2019; 33(3):1-10.
  3. Dunaif A. Polycystic ovary syndrome in 2011: Genes, aging and sleep apnea in polycystic ovary syndrome. Nature Reviews Endocrinology 2011; 8(2):72-4.
  4. Barber TM, Hanson P, Weickert MO, Franks S. Obesity and Polycystic Ovary Syndrome: Implications for Pathogenesis and Novel Management Strategies. Clinical Medicine Insights: Reproductive Health 2019; 9(13):1-9.
  5. Susan K, Christopher R, Kristen, John C. Neuroendocrine Effects of Androgens in Adult Polycystic Ovary Syndrome and Female Puberty. Seminars in Reproductive Medicine 2007; 25(5):352-9.
  6. Mahmoudian A, Dehghan M, Jafarpour M. The effect of morphine administration on structure and ultrastructure of uterus in pregnant mice. Iranian Journal of Reproductive Medicine 2010; 8: 111-8.
  7. Trevor AJ, Masters SB, Katzung BG. Basic& Clinical pharmacology. 14thed. New York: McGraw-Hill Medical 2018.
  8. Lembo PM, Grazzini E, Groblewski T, O'Donnell D, Roy MO, Zhang J, et al. Proenkephalin A gene products activate a new family of sensory neuron-specific GPCRs. Nature Neuroscience 2002; 5(3):201-9.
  9. Hat GK, Mahesh VB, Ping L, Chorich L, Wiedmeier VT, Brann DW. Opioid-glutamate-nitric oxide connection in the regulation of luteinizing hormone secretion in the rat. Endocrinology 1998; 139(3):955-60.
  10. Abs R, Verhelst J, Maeyaert J, Van Buyten JP, Opsomer F, Adriaensen H, et al. Endocrine consequences of long-term intrathecal administration of opioids. The Journal of Clinical Endocrinology & Metabolism 2000; 85:2215-22.
  11. Smith YR, Stohler CS, Nichols TE, Bueller JA, Koeppe RA, Zubieta JK. Pronociceptive and antinociceptive effects of estradiol through endogenous opioid neurotransmission in women. The Journal of Neuroscience 2006; 26(21):5777-85.
  12. Eyvazzadeh AD, Pennington KP, Pop-Busui R, Sowers M, Zubieta JK, Smith YR. The role of the endogenous opioid system in polycystic ovary syndrome. Fertility and Sterility 2009; 92 (1):1-12.
  13. Karami M, Darban Fooladi M, Jalali Nadoushan M, Lakzaei F. Ovarian Polycystic Induction with Morphine in Wistar Rat. Journal of Basic and Clinical Pathophysiology 2015; 3(1):1-6.
  14. Hassani F, Karami M, Jalali Nadoushan MR, Eftekhari Yazdi P. Nitric oxide-induced polycystic ovaries in the Wistar rat. International Journal of Fertility and Sterility 2012; 6(2):111-6.
  15. Karami M, Mohammadi M, Afraz S. Survey on the interaction effect of dopamine D2 receptor antagonist on morphine-induced polycystic ovary syndrome in rat. Daneshvar Medicine 2020; 28(3):16-27
  16. Lakoski JM, Gebhart GF. Attenulation of morphine’s depression of serum luteinizing hormone by lesions inthe amygdale. Neuroendocrinology 1981; 33:105-11.
  17. Sianati S, Sharif B, Sadeghi M, Kalbasi Anaraki D and Dehpour AR. Effects of female sex hormones on morphine dependence. Annals of General Psychiatry 2008; 7(1):264.
  18. Nabatchian F, Tashauoei M, Bahrami A. Evaluation of the Effects of Morphine on Sex Hormones in Wistar Rats. Journal of Laboratory & Diagnosis 2019; 11 (43):42-9.
  19. Tsilchorozidou T, Overton C, Conway GS. The pathophysiology of polycystic ovary syndrome. Clinical Endocrinology 2004; 60:1-17.
  20. Lim DK. Ketamine associated psychedelic effects and dependence. Singapore Medical Journal 2003; 44(1):31-4.
  21. Hashemnia M, Javedani M, Nikoosafat Z, Abdoli Jamoor S. Study of Hematological, Biochemical and Histopathological Changes Due to Long-Term Administration of Ketamine in Rat. Journal of Rafsanjan University of Medical Sciences 2018; 17(7):639-56.
  22. Chakraborty TR, Ng L, Gore AC. Colocalization and hormone regulation of estrogen receptor and N-methyl-D-aspartate receptor in the hypothalamus of female rats. Endocrinology 2003; 144:299-305.
  23. Reyes Toso CF, Linares LM, Rodríguez RR. Blood sugar concentrations during ketamine or pentobarbitone anesthesia in rats with or without alpha and beta adrenergic blockade. Medicina (B Aires) 1995; 55(4):311-6.
  24. Urkler C, Onat T, Yildirim E, Kaplan S, Yazici G, Mammadov R et al. Can the negative effects of ketamine abuse on female genital organs be prevented by nimesulide? An experimental study. General Physiology and Biophysics 2019; 38(5):427-34.
  25. Annetta MG, Iemma D, Garisto C, Tafani C, Proietti R. Ketamin: new indication for an old drug. Current Drug Targets 2005; 6(7):789-94.
  26. Canale TS. Campbell’s operative orthopedics. 9th ed. St. Louis: Mosby 1998.
  27. Kapfer B, Alfonsi P, Guignard B, Sessler DI, Chauvin M. Nefopam and ketamine comparably enhance postoperative analgesia. Anesthesia & Analgesia 2005; 100(1):169-74.
  28. Ottem EN, Godwin JG, Petersen SL. Glutamatergic signaling through the N -methyl-D-aspartate receptor directly activates medial subpopulations of luteinizing hormone-releasing hormone (LHRH) neurons, but does not appear to mediate the effects of estradiol on LHRH gene expression. Endocrinology 2002; 143:4837-45.
  29. Peltoniemi MA, Hagelberg NM, Olkkola KT, Saari TI. Ketamine: A Review of Clinical Pharmacokinetics and Pharmacodynamics in Anesthesia and Pain Therapy. Clinical Pharmacokinetics 2016; 55(9):1059-77.
  30. Yang SS, Jang MY, Lee KH, Hsu WT, Chen YC, Chen WS, et al. Sexual and bladder dysfunction in male ketamine abusers: A large-scale questionnaire study. PLoS One 2018; 13(11):1-10.
Daneshvar Medicine
Volume 29, Issue 3 - Serial Number 154
September and October 2021
Pages 29-41

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