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Neuroendocrine changes in adult female rats prenatally exposed to phenytoin
A Makatsori1, Dubovicky Michal, Ujhazy Eduard
1Laboratory of Pharmacological Neuroendocrinology, Institute of Experimental Endocrinology, Slovak Academy of Sciences, Vlarska 3, Bratislava, 83306, Slovakia.
Insights
Prenatal exposure to phenytoin, an antiepileptic drug, enhances the stress response in adult female offspring. This study found increased catecholamine and corticosterone levels following mild stress, suggesting a new aspect of fetal hydantoin syndrome.
Area of Science:
- Neuroendocrinology
- Developmental Toxicology
- Animal Models
Background:
- Fetal hydantoin syndrome (FHS) is associated with prenatal exposure to phenytoin.
- Neuroendocrine changes in FHS remain largely undescribed.
- The impact of prenatal phenytoin on offspring stress response is unknown.
Purpose of the Study:
- To investigate the effects of prenatal phenytoin exposure on the stress response in adult female offspring using an animal model.
- To assess potential depression-like states, hedonic behavior, and hypothalamic neuropeptide gene expression changes.
Main Methods:
- Pregnant rats received daily oral doses of phenytoin (150 mg/kg) or water from day 7-18 of gestation.
- Adult female offspring were subjected to acute stress (1-minute handling).
- Blood samples were collected to measure catecholamine and corticosterone concentrations before and after stress.
Main Results:
- Prenatal phenytoin exposure led to increased catecholamine and corticosterone levels in adult offspring following mild stress.
- The treatment did not induce depression-like states or long-term changes in neuropeptide gene expression.
Conclusions:
- Prenatal phenytoin exposure enhances the stress response in adult female offspring.
- Increased catecholamine release in adulthood may represent a novel component of fetal hydantoin syndrome.
Abstract:
Neuroendocrine changes in fetal hydantoin syndrome have not been described yet. This study was aimed to verify the hypothesis that prenatal exposure to phenytoin influences the stress response of adult female offspring in an animal model. To study possible development of depression like state, hedonic behavior and long-term changes in neuropeptide gene expression in the hypothalamus were investigated. Treatment consisted of per os administration of 150 mg/kg of phenytoin or water daily, from day 7-18 of gestation. Adult female offspring (6 animals per group) were acutely stressed by 1 min handling. Blood was collected in conscious rats via tail artery cannulas before, 1, 15 and 30 min after the handling. Exposure to phenytoin in uterus resulted in increased catecholamine and corticosterone concentrations in response to a mild stressor of 1 min handling in adult offspring. The gestational treatment used in this study did not induce a depression like state nor long-term changes in neuropeptide gene expression in the adult offspring. In conclusion, prenatal exposure to phenytoin treatment enhanced the stress response of adult female offspring. Possible new component of fetal hydantoin syndrome is the increase in catecholamine release in response to a mild stressor in adulthood.
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