The long-term objective of this research is to develop an animal model of the effects of fetal alcohol in humans. The behavioral features which this model addresses are short- and intermediate-term memory, and learned reactions to novelty, discrepancy, and persistence. This work is based on a body of normative, developmental data in infant rats on the behavioral consequences of consistent, inconsistent, and abruptly changing reward schedules. It also involves measures of heart-rate change in relation to disconfirmation of expectancy. While previous research in adult rats, and our own research in infant rats exposed and not exposed to ethanol, has implicated the hippocampus as an important substrate in memorial effects and reactions to novelty, inconsistency, and persistence, a portion of this research may also be applicable to, and have implications for, a theory of Attention Deficit Hyperactivity Disorder (ADHD). Certain symptoms of this disorder (hyperactivity, distractability) have in some instances been attributed to exposure to ethanol in utero. (In the animal model, human in utero exposure is equivalent to combined prenatal and early postnatal exposure to ethanol, and this manipulation will be emphasized in the present work.) The theory of ADHD which will be tested holds that at least some ADHD-like effects (those related to prenatal ethanol or other toxic substances) result from prolonged, unresolved conflict between approach and avoidance tendencies. This conflict is related to failure of anticipated frustration to be habituated, i.e., to be counterconditioned to approach to the goal. In this research, the behavioral and autonomic measures are complemented by, and correlated with, morphological and neurochemical indices of the effects of ethanol, particularly in the hippocampal formation of the brain. The neuroanatomical measures are number and density of cells in, and areas of, various hippocampal sub-regions; the neurochemical work involves autoradiographic analyses of the effects of ethanol on pyramidal-cell and granule-cell neurogenesis and on beta-adrenergic and muscarinic-cholinergic receptors.
|Diaz-Granados, J L; Spuhler-Phillips, K; Lilliquist, M W et al. (1997) Effects of prenatal and early postnatal ethanol exposure on [3H]MK-801 binding in rat cortex and hippocampus. Alcohol Clin Exp Res 21:874-81|