The proposed research described is designed to examine whether chronic exposure to cocaine in utero results in long-term or residual functional consequences in rhesus monkey offspring as adults. It was determined previously that the ability of cocaine-exposed offspring to learn to perform several complex behavioral tasks at a young age was no different from that of control subjects. A variety of tasks were utilized, including those thought to model aspects of learning, short-term memory, color and position discrimination, timing and motivation. Similarly, data to date suggests that these offspring are not different from controls in their behavioral responses to pharmacological challenges with compounds chosen to interact with specific neurotransmitter systems. These data, thus, suggest that the neural circuity subserving performance of these complex behaviors survives intact and that important neurochemical systems appear to be functioning normally in these animals. Preliminary data recently obtained from a few of the oldest offspring in this group are, however, now suggesting that animals exposed to cocaine in utero are, as adults, showing severe problems making appropriate adjustments to changes in their environment (i.e., changes in the rules of reinforcement associated with the performance of tasks with which they have had extensive history). Such behavioral challenges, or reversals, may prove to be useful tools for unmasking abnormalities in CNS function in subjects that otherwise appear normal. The current application will further explore the robustness and generalizability of these initial findings by changing reinforcement contingencies for several other tasks that the animals have been performing. Should problems with reversal be task specific, then insights into possible neural substrates may emerge, suggesting future interventions. Whether the reversal problems experienced by monkeys exposed to cocaine in utero can be attenuated by specific behavioral manipulations will also be explored. Finally, the current application will systematically explore how long affected subjects must be exposed to specific reinforcement contingencies before reversals of these contingencies manifest as behavioral problems (i.e., how much history of specific tasks performance is required/sufficient to cause subsequent difficulty in subject's ability to adjust its behavior when presented with changing of rules of reinforcement).
| Chelonis, John J; Gillam, Michael P; Paule, Merle G (2003) The effects of prenatal cocaine exposure on reversal learning using a simple visual discrimination task in rhesus monkeys. Neurotoxicol Teratol 25:437-46 |
