Charles W. Bradberry, Ph.D.
Associate Professor, Psychiatry- Ph.D. University of Kansas (1986)
- Office: Biomedical Science Tower 3, Room 4066
- Telephone:412-383-6200
- Fax:412-383-6799
- E-mail: bradberrycw@upmc.edu
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Neurochemical and cognitive traits in primates associated with chronic exposure to drugs of abuse or a predisposition to self-administer them.
Research Summary:
Dr. Bradberry’s research examines neurobiological traits associated with chronic exposure to drugs or alcohol, or ones that predispose individuals to substance abuse. The latter can result either from environmental events or inherent predisposition. Work is conducted in non-human primates because of their similarity to humans in terms of brain size, structure, and function. This permits the use of animal models relevant to human patterns of drug use, or models with features that closely parallel clinical conditions. Currently there are four major projects underway in the laboratory.
1) Study of alterations in corticostriatal function as a result of chronic cocaine self-administration. Work to date has focused on the direct effects of self-administered cocaine, and the effects of cocaine-associated environmental cues. The current focus of this project is to examine alterations in corticostriatal function resulting from chronic cocaine self-administration.
2) Characterization of serotonergic function in a non-human primate model of impulsivity and alcoholism. In both humans and non-human primates, there is a highly replicated observation of an inverse correlation between CSF 5-HT metabolite 5-HIAA and impulsivity, aggression and preference for alcohol. Peer-rearing of rhesus monkeys results in individuals at the extreme of the low 5-HIAA phenotype. Despite a classic interpretation of reduced 5-HT function, there is very little actual work in-vivo to characterize 5-HT function. Studies will employ brain imaging to assess 5-HT transporter ligand binding and compare this with measures of 5-HT release and functional activity of the transporter using microdialysis. Post-mortem measures will determine whole tissue indices of 5-HT innervation and potential metabolic contributions to the low 5-HIAA levels.
3) Preclinical study of agonist approaches for cocaine dependence, focusing on cocaethylene as a model compound. It is equipotent to cocaine at the dopamine transporter, but less potent at the 5-HT and norepinephrine transporters. Human laboratory studies indicate this compound produces less euphoria and cardiovascular effects than equivalent doses of cocaine, and this laboratory has previously demonstrated a rapid tolerance to the behavioral and neurochemical effects of cocaethylene in rodents. We are currently engaged in a comparison of the reinforcing efficacy of cocaethylene and cocaine, using a progressive ratio self-administration approach. Concurrent microdialysis procedures allow a comparison of their neurochemical effects. Because of ongoing investigations of cocaethylene in human laboratory studies, our studies on the behavioral and neurochemical effects of cocaethylene in non-human primates offers an unusual opportunity for insight into the neurochemical basis of cocaine.
4) Mechanisms of D1 dopamine receptor mediated effects on prefrontal cortex function. This project examines the effects o
Selected Publications:
Tokuno, H.A., Bradberry, C.W., Everill, B., Agulian, S.K., Wilkes, S., Baldwin, R.M., Tamagnan, G.D. and Kocsis, J.D. Local anesthetic effects of cocaethylene and isopropylcocaine on rat peripheral nerves. Brain Res. 996(2): 159-67, 2004.
Bradberry, C.W. and Rubino, S.R. Dopaminergic responses to self-administered cocaine in Rhesus monkeys do not sensitize following high cumulative intake. Eur J Neurosci. (10): 2773-8, 2006.
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(3): 705-17, 2007. Epub 2006 Oct 10. Review.