Volume 13, Issue 5 (7-2015)                   IJRM 2015, 13(5): 275-282 | Back to browse issues page

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Ghowsi M, Yousofvand N. Impact of morphine dependency and detoxification by methadone on male’s rat reproductive system. IJRM 2015; 13 (5) :275-282
URL: http://ijrm.ir/article-1-649-en.html
Impact of morphine dependency and detoxification by methadone on male’s rat reproductive system
Mahnaz Ghowsi1 , Namdar Yousofvand * 2
1- Department of Biology, Faculty of Sciences, Razi University, Kermanshah, Iran
2- Department of Biology, Faculty of Sciences, Razi University, Kermanshah, Iran , yousofnam@yahoo.com
Abstract:   (2882 Views)
Background: One of the problems that addicts suffer from is decreased libido. Erectile dysfunction has been reported in men using opioids for treatment of heroin addiction.
Objective: The study was performed to investigate the effects of morphine and detoxification with methadone as causes of sexual dysfunction in addiction.
Methods and Methods: A total of 40 adult male rats (Wistar) were used. Animals were divided in to 4 groups. Control groups received saline for 30 days. Other 2 groups received 10 mg/kg morphine on day 1 and the morphine doses increased daily by 2 mg/kg increments per day until in day 30 a maximum of 68 mg/kg twice daily was achieved. Withdrawal syndrome sings were evaluated. At the end of period, one group of 2 morphine dependent groups was treated with methadone during 14 days. Animals in group 4 (saline solution+ methadone) received saline for 30 consecutive days and then detoxified with methadone during 14 days.  Partial weights of seminal vesicles, testes, prostates, seminal vesicles content, concentrations of luteinizing hormone, follicle stimulating hormone, and testosterone in serum were determined.
Results: In the dependent group serum levels of testosterone (p<0.001), folicle stimulating hormone (p=0.0097) and luteinizing hormone (p=0.0031) as well as the weights of testes (p=0.0051), partial weights of prostates, seminal vesicles and seminal vesicles contents (p<0.001) were reduced as compared with control group. In the morphine dependent animals detoxified with methadone, testosterone concentrations and seminal vesicles contents remained lower than levels in the control group (p<0.001).
Conclusion: The results suggest that morphine dependence may impair the reproductive function in male rats.
Keywords: Morphine, Methadone, Detoxification, Reproductive system, Rat.
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Type of Study: Original Article |
References
1. John B, Griffin JR. Substance Abuse. In Clinical methods. The history, physical and laboratory examinations. 3rd Ed. London; Butterworth; 1990: 922.
2. Rajabizade G, Remezani M, Shakibi M. Prevalence of opium addiction in Iranian drivers. J Med Sci 2004, 4: 210-213. [DOI:10.3923/jms.2004.210.213]
3. Krantz MJ, Mehler PS. Treating Opioid Dependence Growing: Implications for Primary Care. Arch Intern Med 2004, 164: 277-288. [DOI:10.1001/archinte.164.3.277]
4. Deglon JM JL, Imer R. Methadone patients' sexual dysfunctions: Clinical and treatment issues. Heroin Add & Rel Clin Probl 2004, 6: 17-26.
5. Teusch L, Scherbaum N, Bohme H, Bender S, Eschmann-Mehl G, Gastpar M. Different patterns of sexual dysfunctions associated with psychiatric disorders and psychopharmacological treatment. Results of an investigation by semistructured interview of schizophrenic and neurotic patients and methadone-substituted opiate addicts. Pharmacopsychiatry 1995; 28: 84-92. [DOI:10.1055/s-2007-979596]
6. Daniell HW. Hypogonadism in men consuming sustained-action oral opioids. J Pain 2002; 3: 377-384. [DOI:10.1054/jpai.2002.126790]
7. Lakoski JM, Gebhart GF. Attenuation of morphine's depression of serum luteinizing hormone by lesions in the amygdale. Neuroendocrinology 1981; 33: 105-111. [DOI:10.1159/000123212]
8. Cicero TJ, Davis LA, LaRegina MC, Meyer ER, Schlegel MS. Chronic opiate exposure in the male rat adversely affects fertility. Pharmacol Biochem Behav 2002; 72: 157-163. [DOI:10.1016/S0091-3057(01)00751-1]
9. Bennett L, Ratka A. Delta opioid receptors are involved in morphine-induced inhibition of luteinizing hormone releasing hormone in SK-N-SH cells. Neuropeptides 2003; 37: 264-270. [DOI:10.1016/S0143-4179(03)00066-0]
10. Vuong C, Van Uum SHM, O'Dell LE, Lutfy K, Friedman TC. The Effects of opioids and opioid Analogs on Animal and Human Endocrine Systems. Endocr Rev 2010; 31: 98-132. [DOI:10.1210/er.2009-0009]
11. Ministry of Health and Medical Education. Treatment protocol: addiction to opiates with agonist drugs. 2st Ed. Tehran; Ministry of Health and Medical Education; 2005; 14-60. [in Persian]
12. Fessehaye Y, Komen H, Rezk MA, Arendonk JAM, Bovenhuis H. Effects of inbreeding on survival, body weight and fluctuating asymmetry (FA) in Nile tilapia, Oreochromis niloticus. Aquaculture 2007; 264: 27-35. [DOI:10.1016/j.aquaculture.2006.12.038]
13. Cemek M, Büyükokurolu ME, Hazman Ö, Bulut S, Konuk M, Birdane Y. Antioxidant Enzyme and Element Status in Heroin Addiction or Heroin Withdrawal in Rats: Effect of Melatonin and Vitamin E Plus Se. Biol Trace Elem Res 2011; 139: 41-54. [DOI:10.1007/s12011-010-8634-0]
14. Brown RT, Zueldorff M. Opioid substitution with methadone and buprenorphine. Sexual dysfunction as a side effect of therapy. Heroin Addict Relat Clin Probl 2007; 9: 35-44.
15. ABS R, Verhelst J, Maeyaert J, Buyten JV, Opsomer F, Adriaensen H, et al. Endocrine consequences long-term intrathecal administration of opioids. J Clin Endocrinol Metab 2000; 85: 2215-2222. [DOI:10.1210/jcem.85.6.6615]
16. Daniell HW. Opioid endocrinopathy in women consuming prescribed sustained-action opioids for control of nonmalignant pain. J Pain 2008; 9: 28-36. [DOI:10.1016/j.jpain.2007.08.005]
17. Fabbri A, Dufau ML. Hormonal regulation of beta-endorphin in the testis. J Steroid Biochem 1988; 30: 347-352. [DOI:10.1016/0022-4731(88)90121-5]
18. Zhou XF, Xiao BL, Zhang GY, Zhuang LZ. A study of the effect of -EP and naloxone on the function of the hypothalamo-pituit.ary-testicular axis of the rat. J Androl 1990; 11: 233-239.
19. Li S, Pelletier G. Opioid regulation of gonadotropin-releasing hormone gene expression in the male rat brain as studied by in situ hybridization. Neuroreport 1993; 4: 331-333. [DOI:10.1097/00001756-199303000-00027]
20. Gabriel SM, Simpkins JW, Kalra SP, Kalra PS. Chronic morphine treatment induces hypersensitivity to testosterone-negative feedback in castratedmale rats. Neuroendocrinology 1985; 40: 39-44. [DOI:10.1159/000124049]
21. DeBold CR, Nicholson WE, Orth DN. Immunoreactive proopiomelancortin (POMC) peptides and POMC-like messenger ribonucleic acid are present in many rat nonpituitary tissues. Endocrinology 1988; 122: 2648-2657. [DOI:10.1210/endo-122-6-2648]
22. Douglass J, Cox B, Quinn B, Civelli O, Herbert E. Expression of the prodynorphin gene in male and female mammalian reproductive tissues. Endocrinology 1987; 120: 707-713. [DOI:10.1210/endo-120-2-707]
23. Kew D, Kilpatrick DL. Expression and regulation of the proenkephalin gene in rat Sertoli cells. Mol Endocrinol 1989; 3: 179-184. [DOI:10.1210/mend-3-1-179]
24. Cicero TJ, Adams ML, O'connor LH, Nock B. In vivo evidence for a direct effect of naloxone on testicular steroidogenesis in the male rat. Endocrinology 1989; 125: 957-963. [DOI:10.1210/endo-125-2-957]
25. Fabbri A. The role and regulation of testicular opioids: Trends Endocrinol Metab 1990; 1: 117-120. [DOI:10.1016/1043-2760(90)90020-4]
26. Gerendai I, Shaha C, Gunsalus GL, Bardin CW. The effects of opioid receptor antagonists suggest that testicular opiates regulate sertoli and leydig cell function in the neonatal rat. Endocrinology 1986; 118: 2039-2044. [DOI:10.1210/endo-118-5-2039]
27. Adams ML, Sewing B, Forman JB, Meyer ER, Cicero TJ. Opioid-induced suppression of rat testicular function. J Pharmacol Exp Ther 1993; 266: 323-328.
28. Mendelson JH, Meyer RE, Ellingboe J, Mirin SM, McDougle M. Effects of heroin and methadone on plasma cortisol and testosterone. J Pharmacol Exp Ther 1975; 195: 296-302.
29. Willenbring ML, Morley JE, Krahn DD, Carlson GA, Levine AS, Shafer RB. Psychoneuroendocrine effects of methadone maintenance. Psychoneuroendocrinology 1989; 14: 371-391. [DOI:10.1016/0306-4530(89)90007-3]
30. Cicero TJ, Bell RD, Wiest WG, Allison JH, Polakoski K, Robins E. Function of the male sex organs in heroin and methadone users. N Engl J Med 1975; 292: 882-887. [DOI:10.1056/NEJM197504242921703]
31. Cicero TJ, Meyer ER, Bell RD, Koch GA. Effects of morphine and methadone on serum testosterone and luteinizing hormone levels and on the secondary sex organs of the male rat. Endocrinology 1976; 98: 367-372. [DOI:10.1210/endo-98-2-367]
32. Marko M, Romer D. Inhibitory effect of a new opioid agonist on reproductive endocrine activity in rats of both sexes. Life Sci 1983; 33: 233-240. [DOI:10.1016/0024-3205(83)90381-8]
33. Banerjee PP, Banerjee S, Tilly KI, Tilly JL, Brown TR, Zirkin BR. Lobe-specific apoptotic cell death in rat prostate after androgen ablation by castration. Endocrinology 1995; 136: 4368-4376. [DOI:10.1210/endo.136.10.7664656]
34. Justulin LA Jr, Ureshino RP, Zanoni M, Felisbino SL. Differential proliferative response of the ventral prostate and seminal vesicle to testosterone replacement. Cell Biol Int 2006; 30: 354-364. [DOI:10.1016/j.cellbi.2006.01.002]
35. Cicero TJ, Meyer ER, Wiest WG, Olney JW, Bell RD. Effects of chronic morphine administration on the reproductive system of the male rat. J Pharmacol Exp Ther 1975; 192: 542-548.
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