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Updated: May 29, 2026
The Use of Trace Eyeblink Classical Conditioning to Assess Hippocampal Dysfunction in a Rat Model of Fetal Alcohol Spectrum Disorders
Published on: August 5, 2017
A limited access mouse model of prenatal alcohol exposure that produces long-lasting deficits in
Megan L Brady1, Andrea M Allan, Kevin K Caldwell
1Department of Neurosciences, School of Medicine, University of New Mexico, Albuquerque, New Mexico 87131, USA.
Insights
Prenatal alcohol exposure (PAE) in mice led to learning deficits in hippocampal-dependent tasks, mimicking human fetal alcohol spectrum disorder (FASD). This model is valuable for studying PAE-induced cognitive impairments.
Area of Science:
- Neuroscience
- Developmental Biology
- Toxicology
Background:
- Prenatal alcohol exposure (PAE) affects approximately 5% of US children, leading to fetal alcohol spectrum disorder (FASD).
- FASD encompasses a range of physical, behavioral, emotional, and social dysfunctions.
- Understanding PAE's impact requires robust animal models.
Purpose of the Study:
- To develop and characterize a mouse model of limited prenatal alcohol exposure.
- To assess the effects of PAE on maternal behavior and offspring development.
- To investigate PAE-induced learning and memory deficits in offspring.
Main Methods:
- A limited-access model using saccharin-sweetened ethanol solution for C57BL/6J mice during gestation.
- Maternal consumption, blood ethanol levels, litter parameters, and maternal care were measured.
- Offspring were tested on fear conditioning and spatial learning tasks.
Main Results:
- Mothers consumed an average of 7.17 g ethanol/kg/day, with peak blood alcohol levels of 88.3 mg/dl.
- No significant differences were observed in maternal weight, litter size, pup weight, or maternal care.
- Prenatal alcohol-exposed offspring showed deficits in hippocampal-dependent learning tasks, but not in locomotor activity.
Conclusions:
- This mouse model effectively replicates human PAE and associated learning deficits.
- The model serves as a valuable tool for investigating the neurobiological mechanisms of FASD.
- Further research using this model can elucidate strategies for mitigating PAE's cognitive consequences.
Background:
It has been estimated that approximately 12% of women consume alcohol at some time during their pregnancy, and as many as 5% of children born in the United States are impacted by prenatal alcohol exposure (PAE). The range of physical, behavioral, emotional, and social dysfunctions that are associated with PAE are collectively termed fetal alcohol spectrum disorder (FASD).
Methods:
Using a saccharin-sweetened ethanol solution, we developed a limited access model of PAE. C57BL/6J mice were provided access to a solution of either 10% (w/v) ethanol and 0.066% (w/v) saccharin or 0.066% (w/v) saccharin (control) for 4 h/d. After establishing consistent drinking, mice were mated and continued drinking during gestation. Following parturition, solutions were decreased to 0% in a stepwise fashion over a period of 6 days. Characterization of the model included measurements of maternal consumption patterns, blood ethanol levels, litter size, pup weight, maternal care, and the effects of PAE on fear-conditioned and spatial learning, and locomotor activity.
Results:
Mothers had mean daily ethanol intake of 7.17 ± 0.17 g ethanol/kg body weight per day, with average blood ethanol concentrations of 68.5 ± 9.2 mg/dl after 2 hours of drinking and 88.3 ± 11.5 mg/dl after 4 hours of drinking. Food and water consumption, maternal weight gain, litter size, pup weight, pup retrieval times, and time on nest did not differ between the alcohol-exposed and control animals. Compared with control offspring, mice that were exposed to ethanol prenatally displayed no difference in spontaneous locomotor activity but demonstrated learning deficits in 3 hippocampal-dependent tasks: delay fear conditioning, trace fear conditioning, and the delay nonmatch to place radial-arm maze task.
Conclusions:
These results indicate that this model appropriately mimics the human condition of PAE and will be a useful tool in studying the learning deficits seen in FASD.
