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Published on: January 12, 2015
Primidone-induced embryolethality and DRL deficits in surviving offspring
W J Pizzi1, A S Newman, A Shansky
1Neuropsychology Laboratory, Northeastern Illinois University, Chicago 60625, USA. w-pizzi@neiu.edu
Insights
Prenatal exposure to primidone (PRM) was embryolethal in rats. Surviving offspring exhibited behavioral impairments, including learning deficits in males and altered activity patterns in females.
Area of Science:
- Neurobehavioral teratology
- Developmental toxicology
- Pharmacology
Background:
- Primidone (PRM) is an anticonvulsant medication.
- The effects of prenatal PRM exposure on offspring development and behavior are not fully understood.
- Understanding drug effects during gestation is crucial for maternal and child health.
Purpose of the Study:
- To investigate the developmental and behavioral consequences of prenatal primidone exposure in Sprague-Dawley rats.
- To assess the embryolethal effects and potential learning or activity impairments in offspring.
Main Methods:
- Pregnant rats received oral primidone (120 mg/kg) or a vehicle control from gestation days 8-20.
- Evaluated dam weight, birth weight, pregnancy maintenance, and implantation sites.
- Assessed offspring behavior, including exploratory activity and learning acquisition using a DRL-20 operant schedule.
Main Results:
- Primidone exposure significantly reduced pregnancy maintenance (43% vs. 100% in controls), indicating embryolethality.
- No differences in dam weight or offspring birth weight were observed.
- Prenatal PRM exposure led to impaired learning acquisition in males and abolished sex-specific activity increases in females.
Conclusions:
- Prenatal primidone exposure is embryolethal in rats at the tested dose.
- Surviving offspring exhibit specific behavioral deficits, including learning impairments and altered activity patterns.
- These findings highlight potential risks associated with primidone use during pregnancy.
Abstract:
Pregnant Sprague-Dawley rats were administered primidone (PRM) by oral gavage on gestation days 8-20 in doses of 0 or 120 mg/kg. This dose did not produce body weight differences in the dams during the dosing period nor were there differences in the birth weights of the offspring. PRM was embryolethal with only 43% of drug-treated dams maintaining their pregnancies, whereas 100% of the pregnant controls produced offspring. An analysis of resorption sites in PRM-treated dams that did not deliver showed a nearly identical number of implantation sites (12.6) compared to the litter size of controls (12.8) that delivered pups. There were no overall differences in exploratory activity levels between PRM-treated and control animals. However, in the PRM-treated females there was an absence of the sexually dimorphic increase in activity seen in control females when compared to control males. The PRM-treated males showed an impairment in the acquisition of a DRL-20 (differential reinforcement of low rates) operant schedule over a 9-week acquisition period. There were no differences in the total response rates between the groups, suggesting that this is a specific learning deficit and not a performance deficit. The results of these experiments provide evidence that prenatal PRM exposure can be embryolethal and also impair behavior in the surviving rat offspring.
