CNUP Training Faculty

Charles W. Bradberry, Ph.D.

Professor, Psychiatry

Ph.D. University of Kansas (1986)

Office: Biomedical Science Tower 3, Room 4066

Understanding the cognitive consequences of drug addiction at the structural and cellular levels in primates.

Research Summary:

My laboratory is devoted to understanding the neurobiology of addiction to drugs and alcohol in order to help in the development of effective treatment. Within that larger goal, I am focused on illuminating the interplay between direct drug exposure and predisposing traits that are associated with risk of abuse and dependence. Clinical populations of addicted/dependent individuals display cognitive deficits and significant brain structural differences from control populations. What cannot be discerned clinically however, is the extent to which these traits were pre-existent. To address this enduring question, we use non-human primate models in uniquely translational approaches. We have chosen to study primates because the higher level of cognitive development of monkeys and their larger brains permit the design of studies employing imaging and cognitive approaches that parallel human laboratory investigations. With imaging results shown to be in common between monkeys and humans, data from invasive studies in monkeys that build upon those imaging results will have a high degree of clinical validity.

The methods we employ to address our research goals are state of the art, clinically relevant, and unique. We have developed high throughput methodologies based on automated cognitive assessment procedures that allow testing of statistically valid populations of non-human primates. Cognitive and structural studies based on longitudinal sampling prior to and following chronic cocaine self-administration are used for comparison of drug self-administering and control groups. The methods themselves are very similar to those used at single time points in human studies, however, ours is the only laboratory in the world that is currently applying them to longitudinal comparisons in large populations of treated and control animals. This approach can reveal the extent to which exposure per se produces clinically observed deficits. In addition to addressing issues of causation, we are focused on the crucial added component of defining what cellular changes can be identified as potential mediators of cognitive dysfunction. These are assessed during cognitive testing by measures that include single cell electrophysiological methods and measures of regional metabolism across the whole brain using positron emission tomography (PET) imaging. Using these approaches, we will greatly increase our understanding of the changes in brain function associated with drug use. Importantly, we can then use this highly clinically relevant paradigm for exploring the utility of treatment options based on improvement of cognitive deficits.

Selected Publications:

Jedema, H.P., Gianaros, P.J., Greer, P.J., Kerr, D.D., Liu, S., Higley, J.D., Suomi, S.J., Olsen, A.S., Porter, J.N., Lopresti, B.J., Hariri, A.R. and Bradberry, C.W. Cognitive impact of genetic variation of the serotonin transporter in primates is associated with differences in brain morphology rather than serotonin neurotransmission. Mol. Psychiatry, in press.

Baeg, E.H., Jackson, M.E., Jedema, H.P. and Bradberry, C.W. Orbitofrontal and anterior cingulate cortex neurons selectively process cocaine associated environmental cues in the rhesus monkey. J. Neurosci., 29: 11619-27, 2009.

Liu, S., Heitz, R.P., Sampson, A.R., Wei, Z. and Bradberry, C.W. Evidence of Temporal Cortical Dysfunction in Rhesus Monkeys Following Chronic Cocaine Self-Administration. Cerebral Cortex 18: 2109-16, 2008.

Bradberry, C.W. Comparison of acute and chronic neurochemical effects of cocaine and cocaine cues in rhesus monkeys and rodents: focus on striatal and cortical dopamine systems. Rev Neurosci 19: 113-28, 2008.

Bradberry, C.W. Cocaine sensitization and dopamine mediation of cue effects in rodents, monkeys, and humans: Areas of agreement, disagreement, and implications for addiction. Psychopharmacology (Berl) 191: 705-717, 2007.

Bradberry, C.W. and Rubino S.R. Dopaminergic responses to self-administered cocaine in rhesus monkeys do not sensitize following high cumulative exposure. Eur J Neurosci 23: 2773-2778, 2006.