Moderate-Level Prenatal Alcohol Exposure Alters Striatal Dopamine System Function in Rhesus Monkeys

Abstract

These results suggest that the vulnerability of the DA system to the effects of moderate doses of alcohol during gestation depend on the timing of the alcohol exposure. Early-gestation moderate alcohol exposure resulted in a reduction or blunting of dopaminergic function in adulthood, whereas middle to late exposure (without early exposure) either induced the opposite pattern or heightened dopaminergic function. Continuously exposed monkeys showed the largest effect, suggesting that the sooner women stop drinking, the better it is for the fetus.

Sensory Processing Disorder in a Primate Model: Evidence From a Longitudinal Study of Prenatal Alcohol and Prenatal Stress Effects

“…Moreover, prenatal alcohol exposure in rodents has been shown to alter neurotransmitter functioning, including decreased DA uptake, deficits in serotonin reuptake sites, reduced density of NMDA receptor agonist binding sites, altered DA synthesis, and altered behavioral responses to dopaminergic drugs (Druse et al, 1990;Hannigan & Pilati, 1991;Kim & Druse, 1996;Maier, Chen, & West, 1996;Sutherland, McDonald, & Savage, 1997). Our own work has found that prenatal alcohol exposure contributed to altered DA neurotransmitter function in the striatum depending on the gestational timing of the alcohol exposure (Schneider et al, 2005).Because of the susceptibility of the developing brain to alcohol-induced apoptotic neurodegeneration (Ikonomidou et al, 2000), prenatal alcohol exposure could compromise cortical plasticity and therefore, acquisition of adaptive behavioral responses to environmental events. Both human and animal studies have concluded that prenatal alcohol exposure can disrupt myelination, as well as glial cells, which are critical for neuronal myelin development (Burden et al, 2005;Guerri, Pascual, & Renau-Piqueras, 2001;Sowell et al, 2001).…”

“…The second goal was to examine whether prenatal exposure to alcohol, stress, or both would alter withdrawal responses (aversion) to repeated tactile stimulation in rhesus monkeys. Our studies to date indicate that rhesus infants from both prenatal stressand prenatal alcohol-exposed pregnancies exhibited reduced neonatal orienting and motor maturity (Schneider, 1992;Schneider, Moore, & Becker, 2001;Schneider, Roughton, & Lubach, 1997), increased stress hormone reactivity (Clarke, Wittwer, Abbott, & Schneider, 1994;Schneider, Moore, & Kraemer, 2004), learning deficits (Schneider, Moore, & Kraemer, 2001), and altered striatal DA system function (Roberts et al, 2004;Schneider et al, 2005). …”

“…PET imaging was used in order to examine post-synaptic receptor binding (D 2 R) and dopamine synthesis (DAsyn) in the striatum (see Roberts et al, 2004, for details , 1997;Schneider et al, 2005).…”

“…All PET studies were performed as described previously (Roberts et al, 2004, Schneider et al, 2005. Separate scans on different days were used to assess D 2 receptor binding and DAsyn.…”

“…The prenatal alcohol-exposed monkeys were from mothers that voluntarily consumed 0.6 g/kg alcohol, comparable to drinking two drinks throughout pregnancy. We reasoned that these monkeys would be at risk for sensory processing disorder based on a large body of scientific evidence indicating that certain prenatal perturbations could impact an individual's developmental trajectory through altered early brain development, inducing long-lasting effects on behavioral regulation (Coles, Platzman, Lynch, & Freides, 2002;Glover & O'Connor, 2002;Jacobson, Jacobson, Sokol, Chiodo, & Corobana, 2004;Mattson et al, 1999;Streissguth, Bookstein, Sampson, & Barr, 1995;Van den Bergh & Marcoen, 2004;Wadhwa et al, 2002;Willford, Richardson, Leech, & Day, 2004).PET imaging was used in order to examine post-synaptic receptor binding (D 2 R) and dopamine synthesis (DAsyn) in the striatum (see Roberts et al, 2004, for details , 1997;Schneider et al, 2005).We previously reported the results of the PET DA scans in the monkeys involved in this study (Roberts et al, 2004). We found that the prenatal stress condition increased the ratio of D 2 receptor binding to DAsyn compared to controls (Roberts et al, 2004).…”