Dopamine Function After Prenatal Ethanol Exposure

Attention deficit/hyperactivity disorder is a prominent behavioral symptom in children with fetal alcohol spectrum disorders (FASD). Attention problems have been linked to a dysfunction of the mesolimbic/cortical dopamine (DA) systems. Previous research from Dr. Shen’s laboratory showed that prenatal ethanol exposure in rats leads to a persistent reduction in the number of spontaneously active DA neurons in the ventral tegmental area (VTA), the origin of the mesolimbic/cortical DA systems. Therefore, the reduced DA neuron activity may contribute to the dysfunction of the mesolimbic/cortical DA systems and attention problems in individuals with FASD. The reduced number of spontaneously active VTA DA neurons caused by prenatal ethanol exposure is not due to a neuronal loss and can be reversed by acute administration of inhibitory agents such as DA agonists and psychostimulants (e.g. amphetamine, methylphenidate), or by increasing inhibitory input. This led to the hypothesis that prenatal ethanol exposure leads to the reduction in the number of spontaneously active VTA DA neurons by the mechanism of depolarization inactivation Ð cessation of action potentials due to over-excitation. This model predicted qualitative changes in the responses of VTA DA neuron to input signals and terminal DA release and an overall dysregulation of the mesolimbic/cortical systems. In this study, Dr. Shen identified key cellular mechanisms that could mediate the over-excitation in VTA DA neurons. The results should provide better understanding of the neural mechanisms underlying attention problems in individuals with FASD and allow for the development of effective phamacological treatment for attention problems. In addition, it sheds light on potential neural mechanism or the treatment of other mental illnesses, as reduced number of spontaneously active VTA DA neurons by depolarization inactivation is also observed after chronic exposure to drugs of abuse and prenatal stress exposure. Funded by a grant of $641,926 from NIAAA, 2007-2011.