Українська English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2017; 63(2): 17-24


A.G. Reznikov, A.A. Limareva

    State Institution “V.P. Komissarenko Institute of Endocrinology and Metabolism of National Academy of Medical Sciences of Ukraine”, Kyiv


We studied the effect of prenatal administration of methyldopa (400 mg/kg bw per day), a norepinephrine synthesis inhibitor, phenibut (100 mg/kg bw per day), a GABA agonist, and immobilization stress on the background of phenibut on the time of puberty and sexual behavior of male and female rats. Drugs were administered orally to pregnant rats during the last week (15-21 days) of pregnancy. In experiments with prenatal stress, pregnant animals were immobilized for one hour every day during the same period of the pregnancy. Some of them received phenibut 30 min before stressing. Administration of phenibut to non-stressed pregnant animals resulted in acceleration of maturation. Administration of methyldopa or phenibut resulted in disorders of sexual behavior of the male and female offspring. However, phenibut weakened demasculinizing and feminizing effects of prenatal stress on the sexual behavior of males, as evidenced by normalization of the duration of the latent periods and intromissions, the number of mountings with intromission and fewer lordosis reactions. Phenibut administered partially restored the timing of puberty in these animals. The findings suggest the involvement of noradrenergic and GABA-ergic mechanisms in the prenatal programming of sexual behavior of animals, as well as the possibility of preventing sexual disorders in adults, prenatally stressed rats by activating the GABA-ergic receptor. Based on these results and previous studies, the concept of dualistic effects of hormonal and pharmacological neurotropic drugs used during pregnancy was suggested. According to the concept, noradrenergic and GABA-ergic mechanisms can have both damaging or protective effect on the reproductive health of offsprings and their ability to respond to stress.

Keywords: prenatal programming; prenatal stress; puberty; sexual behavior; phenibut; methyldopa; rats.


  1. Messer LC, Boone-Heinonen J, Moonwane L, Wallack L, Thornburg KL. Developmental programming: priming disease susceptibility for subsequent generations. Curr Epidemiol Rep. 2015; 2:37-51. CrossRef PubMed PubMedCentral
  3. Reznikov AG. Hormone-neurotransmitter imprinting in the neuroendocrine control of reproduction. Harwood Acad Publ, Harwood. 1994.
  5. Reznikov AG, Pyshak VP, Nosenko ND, Tkachuk SS, Myslitsky VF. Prenatal stress and neuroendocrine pathology. Tchernovtsy: Medakademia Publishers. 2004. [Russian].
  7. Tkachuk OV, Tkachuk SS, Myslytsky VF. Up-to-date views to brain sexual dimorphism formation and mechanisms of its abnormality. Clin Exper Pathol, 2015;14:248- 53. [Ukrainian].
  9. Vaiserman AM. Epigenetic programming by early- life stress: evidence from human populations. Dev Dyn. 2015; 244:254-65. CrossRef PubMed
  11. Lenz KM, McCarthy MM. Organized for sex-steroid hormones and the developing hypothalamus. Eur J Neurosci. 2010; 32:2096-104. CrossRef PubMed PubMedCentral
  13. Reznikov AG. Preventive neuroendocrinology: this is time for gathering stones. Visnyk NAS Ukraine. 2003; 5:15-22. [Ukrainian].
  15. Salisbury AL, Ponder KL, Padbury JF, Lester BM. Fetal effects of psychoactive drugs. Clin Perinatol. 2009; 36:595–619. CrossRef PubMed PubMedCentral
  17. Hermansen TK, Melinder A. Prenatal SSRI exposure: effects on later child development. Child Neuropsychol. 2015; 21:543-69. CrossRef PubMed
  19. Reznikov A.G., Nosenko N.D., Tarasenko L.V., Limareva A.A. Changes in the brain testosterone metabolism and exual behavior of male rats prenatally exposed to methyldopa and stress. Int J Physiol Pathophysiol. 2016; 7.231-8.
  21. 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;17:393–401. CrossRef  
  22. Canchola E, Rodríguez-Medina M, Due-as-Tentori H. Ca2+-calmodulin system: participation in the progesterone- induced facilitation of lordosis behavior in the ovariectomized estrogen-primed rat. Pharmacol Biochem Behav. 1996; 54:403–7. CrossRef  
  23. Reznikov AG Sex hormones and brain differentiation. Kiev: Naukova Dumka, 1982. [Russian].
  25. Ugrumov MV. Hypothalamic catecholaminergic system in ontogenesis development and functional significance. In: Phylogeny and Development of Catecholamine System (eds. W. Smeets and Reiner T.), London, Cambridge Univ. 1994. [Russian].
  27. Ugrumov MV Neuroendocrine regulations in adult mammalians and during ontogenesis. Fiziol Zhurn. (Ukr.). 2011; 57.84-5. [Russian].
  29. Hull EM, Dominguez JM. Sexual behavior in male rodents. Horm Behav. 2007; 52: 45–55. CrossRef PubMed PubMedCentral
  31. Stratton MS, Staros M, Budefeld T, Searcy BT, Nash C, Eitel C, Carbone D, Handa RJ, Majdic G, Tobet SA. Embryonic GABA(B) receptor blockade alters cell migration, adult hypothalamic structure, and anxiety- and depression-like behaviors sex specifically in mice. PLoS One. 2014; Aug 27;9(8):e106015. CrossRef PubMed PubMedCentral
  33. Barrett ES, Redmon JB, Wang C, Sparks A, Swan, SH Exposure to prenatal life events stress is associated with masculinized play behavior in girls. Neurotoxicol. 2014; 41:20–7. CrossRef PubMed PubMedCentral
  35. Tsipkun AH. Reproductive safety and fetal risk of drugs. 2014; 5:15-20. [Ukrainian].
  37. Reznikov A.G. Animal research on prenatal factors of functional neuroendocrine disorders. Reprod Endocrinol. 2016; N3. 8-15. CrossRef

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2024.