The effect of developmental alcohol exposure on cocaine sensitization acquisition, withdrawal anxiety, and dopamine transporter levels.

摘要

Fetal Alcohol Spectrum Disorder (FASD) occurs in 9 out of every 1000 live births, and is the number one preventable cause of mental retardation in the Western World. Of these children, 20-70% exhibit addiction problems in adolescence and adulthood. Because of this high co-morbidity with addiction problems, it is important to study the underlying mechanisms of addiction in this population. In this experiment, the response to repeated administration of cocaine in a rat model of FASD was examined. Long-Evans rats were pre- and postnatally exposed to alcohol to mimic alcohol exposure during all three trimesters in the human. Control groups consisted of a group exposed to the same administration procedures but not alcohol and a non-treated group. At late adolescence, locomotion in response to cocaine administration was measured after the initial cocaine exposure, after one week of repeated cocaine exposure, and after two weeks of abstinence. After the final testing day, anxiety during the withdrawal period was measured with the elevated plus maze (EPM). The animals were then sacrificed and the Nucleus Accumbens was micropunched so that Dopamine Transporter levels could be assessed through western blotting in whole membrane, plasma membrane, and cytosol fractions. Results suggest that cocaine exposure has an increased effect on locomotion in animals exposed to alcohol during development. Specifically, this effect was seen following a period of abstinence and was stronger in male ethanol-treated animals than female ethanol-treated animals. The enhanced effect of cocaine on locomotion was mirrored in the brain such that ET males had increased cytosol DAT levels compared to all other groups.