An animal model of fetal alcohol spectrum disorder: Trace conditioning as a window to inform memory deficits and intervention tactics

• Published in: Physiology & behavior Vol. 148; pp. 36 - 44
• Main Authors: Hunt, Pamela S, Barnet, Robert C
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2015
• Subjects: Adolescent; Age Factors; Analysis of Variance; Animals; Animals, Newborn; Body Weight - drug effects; Central Nervous System Depressants - toxicity; Child; Choline; Choline - administration & dosage; Conditioning, Classical - drug effects; Disease Models, Animal; Ethanol - toxicity; Fetal alcohol; Fetal Alcohol Spectrum Disorders - etiology; Fetal Alcohol Spectrum Disorders - physiopathology; Humans; Intervention; Memory Disorders - etiology; Memory Disorders - therapy; Nootropic Agents - therapeutic use; Physostigmine; Physostigmine - therapeutic use; Psychiatry; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; Serial compound; Trace conditioning; Intervention; Physostigmine; Fetal alcohol; Trace conditioning; Choline; Serial compound
• ISSN: 0031-9384; 1873-507X
• DOI: 10.1016/j.physbeh.2014.11.066

Abstract Animal models of Fetal Alcohol Spectrum Disorders (FASD) afford the unique capacity to precisely control timing of alcohol exposure and alcohol exposure amounts in the developing animal. These models have powerfully informed neurophysiological alterations associated with fetal and perinatal alcohol. In two experiments presented here we expand use of the Pavlovian Trace Conditioning procedure to examine cognitive deficits and intervention strategies in a rat model of FASD. Rat pups were exposed to 5 g/kg/day ethanol on postnatal days (PD) 4–9, simulating alcohol exposure in the third trimester in humans. During early adolescence, approximately PD 30, the rats were trained in the trace conditioning task in which a light conditioned stimulus (CS) and shock unconditioned stimulus (US) were paired but separated by a 10-s stimulus free trace interval. Learning was assessed in freezing behavior during shock-free tests. Experiment 1 revealed that neonatal ethanol exposure significantly impaired hippocampus-dependent trace conditioning relative to controls. In Experiment 2 a serial compound conditioning procedure known as ‘gap filling’ completely reversed the ethanol-induced deficit in trace conditioning. We also discuss prior data regarding the beneficial effects of supplemental choline and novel preliminary data regarding the pharmacological cognitive enhancer physostigmine, both of which mitigate the alcohol-induced cognitive deficit otherwise seen in trace conditioning controls. We suggest trace conditioning as a useful tool for characterizing some of the core cognitive deficits seen in FASD, and as a model for developing effective environmental as well as nutritional and pharmacological interventions.