Studying dopamine-dependent functions such as memory and creativity can help us understand and improve quality of life in populations at risk for dopaminergic network dysfunction. I examined memory and creativity in a series of studies in different at-risk populations. The first study investigated marijuana initiation and learning in 119 inner-city youth, some with prenatal substance exposures, including to cocaine. I hypothesized that earlier-onset marijuana use would predict poorer developmental learning trajectories, and non-use the most positive. Results suggested that initiation’s effects on learning may reflect psychosocial factors rather than prenatal substance exposure status or time of marijuana initiation. The potential importance of the dopamine-related personality factor “openness to experience” motivated additional studies. One hypothesized and found different neurocognitive outcomes in young-adult substance users (n=41) based on maladaptive or adaptive substance use motives. The other studies examined Parkinson’s disease (PD), a disorder characterized by the degeneration of brain dopaminergic networks. Participants were individuals with PD without dementia (33-42 “PDs”/study), age-matched normal control adults (26-28 “NCs”/study), and younger control adults (37-41 “YCs”/study). The first PD study examined neuropsychological and personality correlates of learning and memory. I hypothesized that in each group, openness would explain a significant amount of the variance in learning, and higher openness would be associated with better learning and memory, particularly in PDs. Results supported this hypothesis in PDs only. The second PD study examined creativity—specifically, divergent thinking, which correlates with openness and shares dopaminergic neural substrates. Based on research demonstrating that brief walking improves divergent thinking in young adults, and that exercise changes dopamine transmission, I hypothesized that brief walking would improve divergent thinking in PDs, NCs, and YCs. In PDs, I expected higher disease severity (more compromised dopamine function) to correlate with less improvement after walking. None of the hypotheses were supported, potentially due to the low intensity of the intervention, but openness appeared protective of creativity in YCs and PDs. Taken together, the results of the studies demonstrate the importance of psychosocial factors in dopamine-dependent cognition. In at-risk populations, openness’s benefits may surpass effects of moderate substance use, and they may offer neuroprotection in PD.