A Quantitative and Qualitative Study of Rat Testis Following Administration of Methadone and Buprenorphine

Abstract

Background: Opiate abuse is a matter of serious concern in adolescent men. The primary drugs used in the treatment of opiate addiction are methadone and buprenorphine. Objectives: This study was undertaken to determine the quantitative and qualitative chang­es in rat testes after methadone and buprenorphine administration. Materials and Methods: In this experimental study, 15 male Wistar rats, each weighing 250 ± 15 g, were selected and randomly divided into 3 groups (n = 5). The first group received an intraperitoneal dose of 0.5 mg/kg/day methadone and the second group received an intraperitoneal dose of 30 mg/kg/day buprenorphine for 15 days each. The third group (control) received normal saline injections. After the last injection dose, the rats were sacrificed and their testes were removed, weighed, and fixed in modified Lillie’s solution, and embedded in 3.5% agar, after which 1-mm slices perpendicular to the long axis of the testes were pre­pared using a tissue slicer. Then, on the basis of Cavaleri’s principle, the testis volume was calculated by point-counting method. For histological analysis, systematic random samples of each testis were selected, processed, and stained by hematoxylin and eosin (H&E) and pe­riodic acid schiff (PAS) methods. The results obtained for the 3 groups were compared using nonparametric Kruskal–Wallis test. P < 0.05 was considered as the level of significance. Results: Stereological analysis of rat testes showed no significant effect of methadone and buprenorphine administration on the testis volume (P > 0.05). However, microscopic stud­ies of rat tissues in the methadone-administered group showed atrophic seminiferous tu­bules, reduction of sperm stem cells, destruction of Sertoli cells, irregularities in the base­ment membrane of seminiferous tubules, cellular degeneration of spermatogonia and primary spermatocytes, and significantly fewer spermatozoids than in the control group. Furthermore, in the methadone-administered group, the germinal cells of seminiferous tubules were damaged and extensively detached from the basement membrane and the vessels of the interstitial tissue were congested. Microscopic studies of the buprenorphine-administered group showed no significant changes in the basement membrane, seminiferous tubules, Sertoli cells, interstitial tissue, and sperms. Conclusions: Buprenorphine is more suitable for treating opiate addiction in males since it does not affect normal testicular structure and function.