Sexual behavior, lipid peroxidation and androgenic function in adult rats following pubertate stress: effects of a GABA agonist or vitamin E
A.G. Reznikov, A.A. Lymareva, O.V. Sachynska, I.G. Perchyk
- State Institution “V.P. Komisarenko Institute of Endocrinology and Metabolism, National Academy of Medical Sciences of Ukraine”, Kyiv
DOI: https://doi.org/10.15407/fz71.04.003

Abstract
Stress-related hormonal imbalances can negatively affect puberty and reproductive function. The aim of our
study was to investigate whether administration of a GABA agonist (phenibut) or vitamin E during puberty
could prevent long-term effects of chronic immobilization stress on oxidative status and sexual behavior
in adult male rat. Adolescent male rats were subjected to daily 1-hour immobilization from postnatal day
30 to 45. Experimental animals received phenibut (100 mg/kg) or vitamin E (50 mg/kg) per os, 30 min-
utes before each stress session. At six months of age, the animals were assessed for male sexual behavior
in the presence of a receptive ovariectomized female primed with estradiol diacetate and progesterone.
Serum testosterone levels were measured, and malondialdehyde and diene conjugate (DC) contents were
determined in testes as markers of lipid peroxidation (LPO). Stressed rats showed increased sexual activ-
ity and copulative capacity. Phenibut administration normalized the number of intromissions but caused
a twofold reduction in serum testosterone and significantly elevated testicular LPO products. In contrast,
vitamin E reduced the latency to first ejaculation without affecting testosterone levels. Although DC levels
were elevated, overall LPO remained unchanged. In conclusion, the use of a GABA agonist (phenibut)
in adolescent male rat has a moderate preventive effect on stress-induced alterations in sexual behavior,
while vitamin E did not demonstrate such an effect. Additionally, phenibut induced oxidative stress in the
gonads and significantly suppressed serum testosterone levels. These findings highlight long-term effects
of phenibut use and underscore the need for caution when prescribing it to adolescents for the treatment
or prevention of anxiety-neurotic condition.
Keywords:
stress, puberty, male rats, sexual behavior, lipid peroxidation, testosterone, phenibut, vitamin E
References
- Bancroft J. Impact of environment, stress, occupational, and other hazards on sexuality and sexual behavior. Environ Health Perspect. 1993 Jul;101 Suppl 2(Suppl 2):101-7. doi: 10.1289/ehp.93101s2101
CrossRef
PubMed PubMedCentral
- Negro-Vilar A. Stress and other environmental factors affecting fertility in men and women: overview. Environ Health Perspect. 1993 Jul;101 Suppl 2(Suppl 2):59-64. doi: 10.1289/ehp.93101s259
CrossRef
PubMed PubMedCentral
- Reznikov AG, Pishak VP, Nosenko ND, Tkachuk SS, Myslitsky VF. Prenatal stress and neuroendocrine pathology. Chernivtsi: Medakademia, 2004.
- Baraboy VA, Reznikov AG. Physiology, biochemistry and psychology of stress. Kyiv: Interservice, 2013. [Ukrainian].
- Reznikov AG. Stress-induced disorders of reproductive functions. Fiziol Zh. 2023;69:97-107. doi: 10.15407/ fz69.06.097. [Ukrainian].
CrossRef
- Reznikov AG. Perinatal programming of the disorders of endocrine function and behavior. Kyiv: Naukova Dumka. 2019. [Ukrainian].
- Casement MD, Shaw DS, Sitnick SL, Musselman SC, Forbes EE. Life stress in adolescence predicts early adult reward-related brain function and alcohol dependence. Soc Cogn Affect Neurosci. 2015 Mar;10(3):416-23. doi: 10.1093/scan/nsu061
CrossRef
PubMed PubMedCentral
- Tordjman S. Aggressive behavior: A language to be under-stood. Encephale. 2022 Sep;48 Suppl 1:S4-S13. Almeida SA, Petenusci SO, Anselmo-Franci JA, Rosa-e-Silva AA, Lamano-Carvalho TL. Decreased spermatogenic and androgenic testicular functions in adult rats submitted to immobilization-induced stress from prepuberty. Braz J Med Biol Res. 1998 Nov;31(11):1443-8. doi: 10.1590/ s0100-879x1998001100013
CrossRef
PubMed
- Strashok LA, Rak LI, Danylenko HM, Yeshchenko AV, Kashina-Yarmak VL, Zavelya EM, et al. Impact of stress on adolescents during puberty (Part 1). Child's Health. 2023;18(5):376-83. [Ukrainian].
CrossRef
- Strashok LA, Rak LI, Danylenko HM, Yeshchenko AV, Kashina-Yarmak VL, Zavelya EM, et al. Impact of stress on adolescents during puberty (Part 2). Child's Health. 2023;18(6):465-73. [Ukrainian].
CrossRef
- Strashok LA, Rak LI, Yeshchenko A V , Kashina-Yarmak VL, Zavelya EM, Isakova MYu. Clinical consequences of psychoemotional stress in adolescence. Child's Health. 2024;19(8):526-32.
CrossRef
- Wommack JC, Salinas A, Melloni RH, Jr, Delville Y. Behavioral and neuroendocrine adaptations to repeated stress during puberty in male golden hamsters. J Neuroendocrinol. 2004 Sep;16(9):767-75. doi: 10.1111/j.1365- 2826.2004.01233.x.
CrossRef
PubMed
- Walker SE, Sandi C. Long-term programming of psycho-pathology-like behaviors in male rats by peripubertal stress depends on individual's glucocorticoid responsiveness to stress. Stress. 2018 Sep;21(5):433-42. doi: 10.1080/10253890.2018.1435639
- A.G. Reznikov, A.A. Lymareva, O.V . Sachynska, I.G. Perchyk 10
CrossRef
PubMed
- Walker SE, Wood TC, Cash D, Mesquita M, Williams SCR, Sandi C. Alterations in brain microstructure in rats that develop abnormal aggression following peripubertal stress. Eur J Neurosci. 2018 Jul;48(2):1818-32. doi: 10.1111/ejn.14061
CrossRef
PubMed
- Harris EP, Villalobos-Manriquez F, Melo TG, Clarke G, O'Leary OF. Stress during puberty exerts sex-specific effects on depressive-like behavior and monoamine neurotransmitters in adolescence and adulthood. Neurobiol Stress. 2022 Oct 3;21:100494. doi: 10.1016/j. ynstr.2022.100494
CrossRef
PubMed PubMedCentral
- Stam JV , Kallen VL, Westenberg PM. Associations be-tween autonomic and endocrine reactivity to stress in adolescence: Related to the development of anxiety? Healthcare. 2023;11(6):869. doi: 10.3390/healthcare11060869.
CrossRef
PubMed PubMedCentral
- Parise LF, Joseph Burnett C, Russo SJ. Early life stress and altered social behaviors: A perspective across species. Neurosci Res. 2023Nov;211:65-74. doi: 10.1016/j. neures.2023.11.005
CrossRef
PubMed PubMedCentral
- Almeida SA, Kempinas WG, Lamano Carvalho TL. Sexual behavior and fertility of male rats submitted to prolonged immobilization-induced stress. Braz J Med Biol Res. 2000 Sep;33(9):1105-9. doi: 10.1590/s0100- 879x2000000900019
CrossRef
PubMed
- Hernández-Arteaga E, Hernández-González M, Bonilla-Jaime H, Guevara MA, Ågmo A. Pubertal stress decreases sexual motivation and supresses the relation between cerebral theta rhythms and testosterone levels in adult male rats. Brain Res. 2020 Oct 15;1745:146937. doi: 10.1016/j.brainres.2020.146937
CrossRef
PubMed
- Sachynska OV, Faliush OA, Perchyk IG, Lymareva AA, Reznikov AG. Stress during puberty exerts longlasting sex-specific reproductive effects in adult rats. Fiziol Zh. 2024; 70(4):3-10. doi: CrossRef fz70.04.003
CrossRef
- Almeida SA, Petenusci SO, Anselmo-Franci JA, Rosa-e-Silva AA, Lamano-Carvalho TL. Decreased spermatogenic and androgenic testicular functions in adult rats submitted to immobilization-induced stress from prepuberty. Braz J Med Biol Res. 1998 Nov;31(11):1443-8. doi: 10.1590/s0100-879x1998001100013
CrossRef
PubMed
- Kaplowitz ET, Savenkova M, Karatsoreos IN, Romeo RD. Somatic and neuroendocrine changes in response to chronic corticosterone exposure during adolescence in male and female rats. J Neuroendocrinol. 2016 Feb;28(2):12336. doi: 10.1111/jne.12336
CrossRef
PubMed
- Almeida SA, Petenusci SO, Franci JA, Rosa e Silva AA, Carvalho TL. Chronic immobilization-induced stress increases plasma testosterone and delays testicular maturation in pubertal rats. Andrologia. 2000 Jan;32(1):7-11.
CrossRef
PubMed
- Reznikov AG, Lymareva AA, Sachynska OV . Modulation of sexual behavior and indicators of oxidative stress in the testes of adult rats as a consequence of chronic stress during puberty. Endokrynologia. 2024; 30(2): 119-25. doi: https:// CrossRef
- Holson RR, Gough B, Sullivan P, Badger T, Sheehan DM. Prenatal dexamethasone or stress but not ACTH or corticosterone alter sexual behavior in male rats. Neurotoxicol Teratol. 1995 Jul-Aug;17(4):393-401. doi: 10.1016/0892-0362(94)00074-n
CrossRef.1016/0892-0362(94)00074-N
PubMed
- Hull EM, Dominguez JM. Sexual behavior in male rodents. Horm Behav. 2007 Jun;52(1):45-55. doi: 10.1016/j. yhbeh.2007.03.030
CrossRef
PubMed PubMedCentral
- Lemeshko VV, Nikitchenko IuV, Svich IV, Ovsiannikov SE. Peroxidation of biomembrane lipids and its enzymatic regulation during aging in the rat. Ukr Biokhim Zh. 1987 Mar-Apr;59(2):50-7.
- Sinclair D, Purves-Tyson TD, Allen KM, Weickert CS. Impacts of stress and sex hormones on dopamine neurotransmission in the adolescent brain. Psychopharmacology (Berl). 2014 Apr;231(8):1581-99. doi: 10.1007/ s00213-013-3415-z
CrossRef
PubMed PubMedCentral
|