The Effects of Cocaine on Nonhuman Primate Brain Function Are Age Dependent^a

The effects of acute intravenous (i.v.) cocaine (COC) on several complex brain functions were studied in rhesus monkeys at 1.5, 3 and 10-11 years of age. Subjects performed several operant tasks (for food) that were used to model learning, short-term memory, color and position discrimination, and motivation, and disruption of performance of these tasks was used to quantitate drug effect. Drug effects were age dependent: The youngest subjects were 3 to 10 times less sensitive than the oldest. Presuming the observed behavioral effects of cocaine were caused primarily via its interaction with dopamine (DA) systems, changes in sensitivity to its effects with age are likely a reflection of the functional status of the DA system. These data, along with preliminary data on levels of DA transporters, suggest that the age-related differences in sensitivity to cocaine lie in, or 'downstream' from, the dopamine receptor.