Low-Dose Stimulant Treatment During Periadolescence in a FASD Model: Interactions Among the Catecholamines

One of the most common of deficits observed in Fetal Alcohol Spectrum Disorders (FASD) is difficulties with attention. Because attention deficits are commonly treated with stimulants, the impact of d-amphetamine (AMPH) treatment during the juvenile period in an animal model of FASD was examined. A dose-response study first assessed the appropriate dose of AMPH to use. In the dose-response study, therapeutic doses of 0.5, 1.0, and 2.0 mg/kg/day of AMPH were chronically administered to female rats between postnatal days (PD) 26-40. Rats were subjected to an open field test on the first and last day of treatment. The dose of 1.0 mg/kg/day was the lowest dose which resulted in significant behavioral sensitization and therefore was selected for the FASD study. In the FASD study, pups were exposed to alcohol between PD 2 and 10. Control groups included an intubated control (IC) and a non-treated control (NC). At PD 26, rats were randomly assigned to either amphetamine or water treatment for twice-daily subcutaneous injections from PD 26 to 41. On PD 26, 27, 40, and 41, an open field test was administered to assess locomotion. On PD 42, the rats were perfused, and the brains were removed and prepped for histological measures. The results indicated that amphetamine increased distance traveled acutely, and that this effect became greater over days of treatment. Amphetamine-treated rats exhibited significantly more rearing behaviors and less grooming behavior than water-treated rats. Both rearing and grooming behavior decreased over test days. There was no effect of alcohol exposure on any open field measures. Dopaminergic and noradrenergic systems were analyzed via immunohistochemistry for tyrosine hydroxylase (TH), the dopamine transporter (DAT) and dopamine-beta-hydroxylase (DBH). An omnibus ANOVA revealed no impact of alcohol exposure or amphetamine treatment on TH or DAT within the nucleus accumbens core. Although amphetamine treatment caused a small but significant increase in DBH within the medial prefrontal cortex, there was no effect of alcohol exposure on this measure. These results suggest that catecholaminergic neurons are resistant to the developmental impact of alcohol. However, juvenile amphetamine treatment may increase noradrenergic synthesis or innervation within the prefrontal cortex, influencing developmental trajectories.