Effects of Alprazolam on the Follicular Development of Rat Ovaries

Document Type : Original Article

Authors

1 Associate Professor, Department of Anatomical and Histological Science, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

2 Associate Professor, Department of Pharmacology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

3 Graduated Student of Veterinary Medicine, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.

Abstract

Introduction: Alprazolam is a benzodiazepine with several applications due to its pharmacological effects. Alprazolam is mostly used in the treatment of anxiety disorders. Alprazolam affects the brain and many other organs. Due to the excessive use of this drug, especially by women, the present study aimed to investigate the effects of alprazolam on the growth and development of ovarian follicles in female rats.
Methods: This applied research was conducted on 24 adult female rats in 2015. Animals were randomly divided into four groups of six. In the first group, alprazolam was administered orally for 16 consecutive days (2 mg/kg). In the second and third group, alprazolam was administered orally for 16 consecutive days at doses of 4 and 6 mg/kg. Rats in the control group received water with the same volume and mode of administration at the same time as the test animals.
Results: Histomorphological studies revealed that high doses of alprazolam (4 and 6 mg/kg) significantly decreased the number of graafian follicles (P<0.05). However, the number of atretic follicles significantly increased in the test groups (P<0.05).
Conclusion: According to the results, high doses of alprazolam affected the follicular development of rat ovaries and may have adverse effects on the fertility of female rats.

Keywords


  1. Vizhe H. Pharmacology. 3rd ed. Tehran. Kalemeh Publication; 1989. P. 197-200. (Persian).
  2. Hanson SM, Czajkowski C. Structural mechanisms underlying benzodiazepine modulation of the GABAA receptor. J Neurosci 2008; 28(13):3490-9.
  3. Watanabe M, Maemura K, Kanbara K, Tamayama T, Hayasaki H. GABA and GABA receptors in the central nervous system and other organs. Int Rev Cytol 2002; 213:1-47.
  4. Yondea Y, Kuriyama K. GABA and endocrine regulation relation to neurologic-psychiatric disorders. Neurochem Int 1984; 6(1):23-6.
  5. Woods JH, Katz JL, Winger G. Benzodiazepines: use, abuse, and consequences. Pharmacol Rev 1992; 44(2):151-347.
  6. Laurijssens BE, Greenblatt DJ. Pharmacokinetic-pharmacodynamic relationships for benzodiazepines. Clin Pharmacokinet 1996; 30(1):52-76.
  7. Erdö SL, Lapis E. Bicuculline-sensitive GABA receptors in rat ovary. Eur J Pharmacol 1982; 85(2):243-6.
  8. Erdõ SL, Varga B, Horváth E. Effect of local GABA administration on rat ovarian blood flow, and on progesterone and estradiol secretion. Eur J Pharmacol 1985; 111(3):397-400.
  9. Belelli D, Bolger MB, Gee KW. Anticonvulsant profile of the progesterone metabolite 5α-pregnan-3α-ol-20-one. Eur J Pharmacol 1989; 166(2):325-9.
  10. Twyman RE, Macdonald RL. Neurosteroid regulation of GABAA receptor single-channel kinetic properties of mouse spinal cord neurons in culture. J Physiol 1992; 456:215-45.
  11. File SE. The history of benzodiazepine dependence: a review of animal studies. Neurosci Biobehav Rev 1990;14(2):135-46.
  12. Guthrie HD, Grimes RW, Cooper BS, Hammond JM. Follicular atresia in pigs: measurement and physiology. J Anim Sci 1995; 73(9):2834-44.  
  13. Dennerstein L, Callan A, Warne G, Montalto J, Brown J, Burrows G, et al. The effects of benzodiazepines on hormones in women with idiopathic hirsutism. Prog Neuropsychopharmacol Biol Psychiatry 1984; 8(1):11-7. 

Takzare N, Bakhtiarian A, Saeedi E, Nekoui V. The teratogenic effects of alprazolam intake on rat fetus. Tehran Univ Med J 2011; 68(10):578-82. (Persian)