NIH Announces the Availability of Recovery Act Funds for Competitive Revision Applications (NOT-OD-09-058). The central question addressed by this Competitive Revision Application is whether prenatal exposure to moderate level alcohol alters the levels of biogenic amines in brain regions and consequently alters the predisposition to consume alcohol during adulthood in a unique cohort of well-characterized prenatal alcohol- exposed adult monkeys. Thirty-two adult rhesus monkeys in this study were born to mothers that consumed alcohol during early gestation (0 - E50), middle-to-late gestation (E50 - E135), or throughout pregnancy (0 - E135), or to sucrose-solution-consuming controls. Because women often drink alcohol before pregnancy is detected, we believe that it is important to study the effects of early gestational exposure, compared to later or continuous exposure, on alcohol consumption in a carefully controlled laboratory setting with a species similar to humans. In the parent project, we use the model of oral alcohol self-administration established by Dr. Kathleen Grant and colleagues that reliably produces a pattern of excessive alcohol consumption in monkeys (Vivian et al., 2001). We use the radiotracers [F-18]FECNT to assess DAT binding, fallypride to assess D2R binding and the D1 ligand [C-11]SCH23390 to assess D1R binding prior to and after chronic alcohol consumption. We are requesting funding to assess the serotonin system through in vivo PET radioligand measures of the 5-HT1A system using [F-18]Mefway binding in hippocampus, cingulate gyrus, and raphe nuclei before and after drinking. Dr. Brad Christian, co-investigator on the parent grant, has shown high uptake of the 5-HT1A PET radiotracer [F-18]Mefway in these regions in rhesus macaques. The rest of the project would proceed as originally described and approved. The overall outcome will produce information from 32 PET scans on 16 monkeys (before and after chronic alcohol consumption) that have been well-characterized behaviorally and genetically. We believe that we have an extraordinary opportunity to accelerate our understanding of the underlying neurobiology associated with chronic alcohol consumption, and to create new jobs, meeting the NIH goals of the American Recovery Act.
Our data show that early gestation exposure, before pregnancy is detected, can alter behavior and brain chemistry in the offspring. The public should be educated about risk factors before pregnancy is detected. Professional training for service providers in the public health sector should include information on possible risk factors for altered behavior and neurochemistry and possible gene x alcohol effects on DA and 5HT function.
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