AA10079 has supported 9 years of nonhuman primate studies to increase our understanding of the mechanisms underlying moderate level prenatal alcohol effects. This project has assessed the effects of moderate level alcohol exposure during specific gestation periods and how prenatal alcohol exposure interacts with prenatal stress to affect offspring neurobehavioral and brain dopamine system function. This continuation project will focus on 40 monkeys exposed to alcohol during the following gestation periods: 1) conception through day 50, 2) gestation days 50 -135, and 3) conception through day 135. These monkeys have been followed since birth and have been well-characterized behaviorally. PET studies have found that FA-exposure-induced effects on striatal DA synthesis and D2-type receptor binding depends upon the timing and duration of alcohol exposure.
Specific Aim 1 will assess serotonin 5-HT1A receptor and 5-HT transporter binding using PET imaging, and develop and pilot 5-HT2 receptor ligands, based on rat findings of alcohol- related abnormal development of the serotonin system.
Specific Aims 2 will assess the binding of D2 receptors in the prefrontal cortex, caudate, putamen, and ventral striatum, and assess performance on an executive function test that is dependent on these regions.
Specific Aim 3 will examine DA D2 receptor occupancy after a CNS challenge with amphetamine to examine function of the DA system under dynamic conditions.
Specific Aim 4 will examine habitation to repeated tactile stimuli and prepulse inhibition, based on the role of dopaminergic pathways underlying sensorimotor gating as well as clinical evidence of unusual sensory sensitivities in fetal alcohol-exposed children.
Specific Aim 5 will develop assays to assess GABAA receptor binding and scan a subset of monkeys based on rodent findings of abnormal GABAA receptors following developmental alcohol exposure. The scientific significance of this work will increase our understanding of brain abnormalities and neurobiological pathways underlying fetal alcohol-induced impairments in cognition and behavior. The clinical importance of this longitudinal research is that it may lead to innovative models for screening tests and interventions, which, when used with other information on maternal alcohol consumption, may facilitate early identification and the development of effective clinical and educational interventions for children at risk for alcohol-related neurodevelopmental disorders.
Showing the most recent 10 out of 26 publications
