Children born to women who cannot control their intake of alcohol can have various alcohol-related birth defects (ARBDs), including Fetal Alcohol Syndrome (FAS). The features of these ARBDs/FAS include characteristic facial anomalies, growth retardation, and Central Nervous System (CNS) dysfunction. The CNS dysfunction is expressed as mental retardation nd developmental delay, learning disabilities and various attentional deficits including hyperactivity, poor vigilance and impulsivity. We have used an animal model of ARBDs that displays many of the features found in children, including growth retardation, overactivity and poor learning and memory. Since attentional deficits in children are often treated with CNS stimulant drugs, such as methylphenidate or amphetamine, we have assessed the biobehavioral responses of animals exposed prenatally to alcohol to challenge doses of CNS stimulants. Rats exposed prenatally to alcohol show increased sensitivity to the behavioral activating effects of amphetamine. In the proposed research, we will examine in more detail the nature of gender influences, behavioral specificity, developmental course, and presumed neural substrates for the effects of prenatal alcohol on these responses. All of these factors are potentially important aspects of any therapeutic regime with CNS stimulants that may be used with FAS children. The proposed research will study the maturation of locomotor, stereotypic and cataleptic responses to dopaminergic drugs in male and female offspring of alcohol-exposed dams. Dopamine agonists and antagonists specific for the D1 or D2 dopamine receptor subtypes will be administered by intracranial injections into dopamine system terminal brain ares, specifically, the neostriatum and the nucleus accumbens. These experiments will help define the functional status of prenatal alcohol-affected dopamine systems, and the results will form a basis for determining how behavioral ARBDs might be treated in FAS children with CNS stimulants or other agents.
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