Rustamova M. F.

ASSESSMENT OF THE INFLUENCE OF CERTAIN NEUROLEPTICS ON THE STATE OF PREGNANT FEMALES AND OFFSPRING DEVELOPMENT IN ONTOGENESIS


About the author:

Rustamova M. F.

Heading:

CLINICAL AND EXPERIMENTAL MEDICINE

Type of article:

Scentific article

Annotation:

Goal. Study of the effect of a typical antipsychotic, a derivative of butyrophenone-haloperidol and an atypical antipsychotic derivative of dibenzodiazepine-clozapine on the state of maternal rats during pregnancy and on the processes of postnatal development of rat offspring in ontogenesis. Methods. Experiments were carried out on 30 female rats and 30 offspring of baby rats, divided into 4 groups. The first group of rats is a control group born from rats of mothers who received 0.2 ml of 0.9% sodium chloride solution intragastrically from the 6th to the 20th days of pregnancy. The second and third groups of rats were experimental, born from rats of mothers who received intraperitoneal haloperidol (Gideon Richter, Hungary) from the 6th to the 20th days of pregnancy, respectively at doses of 0.5 and 3 mg/kg. The fourth group of baby rats-experienced, born from rats of mothers who received orally from the 6th to the 20th days of pregnancy the drug clozapine (Kiev vitamin plant, Ukraine) at a dose of 10 mg/kg. In experiments, the condition of female rats was monitored during pregnancy until delivery. In animals, the General condition was noted, the dynamics of body weight gain, the duration of pregnancy, and the course of childbirth were recorded. Observations of the offspring were carried out from the moment of birth to 2 months of age. Indicators of physical development of rat pups, such as peeling of the ear, hair growth, incisor eruption, eye opening and formation of sensory-motor reflexes – the «negative geotaxis» test, were registered visually. Results. Analysis of the pregnancy course of experimental females showed that the duration of pregnancy in the experimental group of animals decreases relative to the control group. Thus, the appearance of offspring in the control group was registered on the 22nd day of pregnancy. Administration of haloperidol at a dose of 0.5 mg/kg and 3 mg/kg contributed to a reduction in the duration of pregnancy of females by 1.75 and 3.45 days, respectively. Administration of clozapine at a dose of 10 mg/kg led to a reduction in the duration of pregnancy by 1.25 days. At the same time, the trends of decreasing body weight gain in the experimental group of female rats were noted. Thus, the weight gain on the 20th day of pregnancy in the control group was 295.9±1.9 g, while in the experimental group of females (haloperidol 0.5 mg/kg) – 270.2±1.2 g. The weight Gain of females in the experimental group haloperidol 3 mg/kg was 12% less than in the control group; in the experimental group clozapine 10 mg/kg – by 5.8%. Thus, from the results of observations, it can be assumed that the drugs haloperidol and clozapine, administered to pregnant rats from the 6th day of pregnancy to delivery, has a significant effect on the General condition of preg-nant women, contributes to the trends of reducing their pregnancy duration, which went beyond the limits of the physiological norm. And this, in turn, is one of the main factors that cause many complications in offspring. Haloperidol in doses of 0.5 mg/kg and 3 mg/kg for intraperitoneal administration, and clozapine in a dose of 10 mg/kg for intrahastric administration have a damaging effect on the General condition of females and negatively affect the postnatal development of their offspring. Postnatal rat babies whose mothers were given haloperidol and clozapine during organogenesis had slower incisor formation, eye opening, sensory-motor reflexes, and delayed puberty. Conclusion. When compared with clozapine, haloperidol has a more pronounced damaging effect on the General condition of females and the physical development of their offspring.

Tags:

antipsychotics, pregnant rats, offspring.

Bibliography:

  1. Direktiva 2010/63/ EU evropejskogo parlamenta i soveta Evropejskogo sojuza po ohrane zhivotnyh, ispol’zuemyh v nauchnyh celjah. SPb.: 2012. 48 s. [in Russian].
  2. Prusakov VF, Morozova EA, Marulina VI, Utkuzova MA, Belousova MV, Zajkova FM. Perinatal’naja patologija mozga i ejo posledstvija. Prakticheskaja medicina. 2010;2(41):46-50. [in Russian].
  3. Markova IV, Afanas’ev VV, Cybul’kin JeK. Klinicheskaja toksikologija detej i podrostkov. Tom 2. SpB.: Intermedika; 1999. 400 s. [in Russian].
  4. Mironov AN, redaktor. Rukovodstvo po provedeniju doklinicheskih issledovanij lekarstvennyh sredstv. Ch. 1. M.: 2012. s. 80-92. [in Russian].
  5. Bajbarina EN, Degtjarev DN. Perinatal’naja medicina: ot teorii k praktike. Rossijskij vestnik perinatologii i pediatrii. 2013;5:4-7. [in Russian].
  6. Arnon J. The use of psychiatric drugs in pregnancy and lactation. J. Psychiatry Relat Sci. 2000;37(3):205-22.
  7. Birnbaum CS, Stowe ZN. Serum concentrations of antidepressants and benzodiazepines in nursing infants: a case series. Pediatrics. 1999;104(11):11.
  8. Burt VK, Suri R, Altshuler L, Stowe Z, Hendrick VC, Muntean E. The use psychotropic medications during breast-feeding. Am J. Psychiatry. 2001;158(7):1001-9.

Publication of the article:

«Bulletin of problems biology and medicine» Issue 2 (156), 2020 year, 158-162 pages, index UDK 615.017:616.079; 615.2/.3.001.37

DOI: