Fetal alcohol syndrome: early olfactory learning as a model system to study neurobehavioral deficits

Abstract

The goal of basic research examining the deficits underlying fetal alcohol syndrome is to develop an animal model which allows investigation and assessment of the neural and cognitive impairments resulting from prenatal alcohol exposure. The following review focuses on animal models and their relationship to human deficits following prenatal alcohol exposure. In addition, this review examines a unique, well-established model system which may permit an increased understanding of the role of alcohol on the developing brain and cognitive behavior. Specifically, large metabolic, neurochemical, neuropharmacological, morphological and neurophysiological changes in young rats have been reported as a consequence of early olfactory preference conditioning, a form of learning that normally occurs during both human and rat development. This olfactory odor preference training paradigm can be used to assess changes in learning as well as the neural substrates underlying this learning. Olfactory preference training has been used to examine: 1) learning, as demonstrated by a behavioral preference for an odor previously paired with stimulation which mimics maternal care; 2) metabolism, by measuring 2-deoxyglucose uptake and distribution in response to the trained odor; 3) neurotransmitter levels, by using in vivo microdialysis, to examine changes in neurotransmitter levels in the olfactory bulb in response to a trained odor. Using in vivo microdialysis enables measurement of both baseline responsiveness of alcohol-exposed pups as well as learned responses at several different developmental ages. The established neural features of this olfactory model include an increase in behavioral preference for a trained odor, increases in 2-DG uptake in specific foci within the olfactory bulb in response to the odor, and increases in dopamine in response to olfactory preference training stimuli, as well as conditioned increases in norepinephrine following olfactory preference training. Using these known behavioral, metabolic and neurochemical indices in control pups allows identification of some of the neurotransmitter systems involved in deficits and the neurobiological basis for impairments induced by prenatal alcohol exposure.