CNUP Training Faculty

Charles W. Bradberry, Ph.D.

Professor, Psychiatry

Ph.D. University of Kansas (1986)

Office: Biomedical Science Tower 3, Room 4066
Telephone:412-383-6200
Fax:412-383-9061
E-mail: bradberr@pitt.edu
Website:

Understanding the cognitive consequences of cocaine use at the structural and cellular levels in primates.

Research Summary:

My laboratory is devoted to understanding the cognitive consequences of cocaine use and the underlying neurobiological mechanisms. 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.

We employ 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, our laboratory is unique in 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 are expanding 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:

Narendran, R, Jedema, H.P., Lopresti, B.J., Mason, N.S., Himes, M.L. and Bradberry, C.W. Decreased vesicular monoamine transporter type 2 availability in the striatum following chronic cocaine self-administration in nonhuman primates. Biol Psychiatry, in press.

Porter, J.N., Minhas, D., Lopresti, B.J., Price, J.C. and Bradberry, C.W. Altered cerebellar and prefrontal cortex function in rhesus monkeys that previously self-administered cocaine. Psychopharmacology, in press.

Narendran, R., Jedema, H.P., Lopresti, B.J., Mason, N.S., Gurnsey, K., Ruszkiewicz, J., Chen, C.-M., Deuitch, L., Frankle, G. and Bradberry, C.W. Imaging dopamine transmission in the frontal cortex: a simultaneous microdiaysis and [11C]FLB 457 PET study, Molecular Psychiatry, 19:302-10, 2014.

Clark, K.H., Wiley, C.A. and Bradberry, C.W. Psychostimulant Abuse and Neuroinflammation: Emerging Evidence of Their Interconnection, Neurotoxicity Research, 23: 174-88, 2013.

Porter, J.N., Olsen, A.S., Gurnsey, K., Dugan, B.P., Jedema, H.P. and Bradberry, C.W. Chronic cocaine self-administration in rhesus monkeys: impact on associative learning, cognitive control, and working memory, J. Neurosci., 31: 4926-4934, 2011.

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.