Neonatal ethanol exposure impairs long-term context memory formation and prefrontal immediate early gene expression in adolescent rats

• Published in: Behavioural brain research 2019-02, Vol.359, p.386-395
• Main Authors: Heroux, Nicholas A., Robinson-Drummer, Patrese A., Kawan, Malak, Rosen, Jeffrey B., Stanton, Mark E.
• Format: Article
• Language: English
• Subjects: Animals; Animals, Newborn; Central Nervous System Depressants - adverse effects; Conditioning, Psychological - drug effects; Conditioning, Psychological - physiology; Context learning; Context preexposure facilitation effect; Development; Disease Models, Animal; Ethanol - adverse effects; FASD; Fear - drug effects; Fear - physiology; Female; Fetal Alcohol Spectrum Disorders - metabolism; Fetal Alcohol Spectrum Disorders - psychology; Genes, Immediate-Early; Hippocampus; Hippocampus - drug effects; Hippocampus - growth & development; Hippocampus - metabolism; Male; Memory - drug effects; Memory - physiology; Neonatal ethanol exposure; Prefrontal cortex; Prefrontal Cortex - drug effects; Prefrontal Cortex - growth & development; Prefrontal Cortex - metabolism; Random Allocation; Rats, Long-Evans; Sexual Maturation
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2018.11.018

•In the CPFE, developmental alcohol exposure abolishes postshock and retention freezing.•Ethanol impairs prefrontal but not hippocampal gene expression during context exposure.•Ethanol exposure has no effect on freezing in standard contextual fear conditioning.•Evidence for prefrontal cognitive impairment in an animal model of FASD. Fetal alcohol exposure leads to severe disruptions in learning and memory involving the hippocampus and prefrontal cortex in humans. Animal model research on FASD has documented impairment of hippocampal neuroanatomy and function but animal studies of cognition involving the prefrontal cortex are sparse. We have found that a variant of contextual fear conditioning in which both the hippocampus and prefrontal cortex is required, the Context Preexposure Facilitation Effect (CPFE), is particularly sensitive to neurobehavioral disruption caused by neonatal ethanol exposure during the third trimester equivalent of human pregnancy in the rat (i.e., PD4-9). In the CPFE, learning about the context, acquiring a context-shock association, and retrieving contextual fear are temporally separated across three days. The current study asked whether neonatal alcohol exposure impairs context learning, consolidation, or retrieval and examined prefrontal and hippocampal molecular signaling as correlates of this impairment. Long-Evans rats that received oral intubation of ethanol (AE; 5.25 g/kg/day, split into two doses) or underwent sham-intubation (SI) from PND4-9 were tested on the CPFE on PD31-33. Extending our previous reports, ethanol abolished both post-shock and retention test freezing in the CPFE. Assays (qPCR) of immediate early gene expression revealed that ethanol disrupted prefrontal but not hippocampal expression of c-Fos, Arc, Egr-1, and Npas4 during context learning. Finally, ethanol-exposed animals were unimpaired in a standard contextual fear conditioning procedure in which learning about the context and acquiring a context-shock association occurs concurrently. These findings implicate impaired prefrontal function in cognitive deficits arising from 3rd-trimester equivalent alcohol exposure in the rat.