Pharmacology and Toxicology - Research

Kathryn A. Cunningham, Ph.D.

Professor

Chauncey Leake Distinguished Professor of Pharmacology
Vice Chairman, Department of Pharmacology and Toxicology
Director, Center for Addiction Research


Research Interests

Our laboratory is studying serotonin (5-HT) plasticity and involvement in vulnerability to addiction and relapse. We are currently testing the hypothesis that an imbalance in 5-HT2 receptor function measured by genetic (e.g., 5-HT2R gene polymorphisms), biological (e.g., 5-HT function in platelets and brain) and endophenotypic variables (e.g., impulsivity, compulsivity) contributes to addiction and the challenges of sustaining abstinence.

We believe the imbalance will be amenable to normalization through new, selective serotonergic ligands constructed based upon our advancing understanding of the cellular and molecular biology of the 5-HT system. This project integrates new knowledge, perspectives and tools across the boundaries of clinical science, chemistry, animal behavior and cellular and molecular biology.

The technologies in use in my lab include animal models of addiction and other psychiatric disorders including transgenic mice (Emeson lab, Vanderbilt), protein (Westerns, immunohistochemistry, co-immunoprecipitations) and RNA evaluations (qRT-PCR, deep sequencing), intracranial microinjection, pharmacological evaluation of new chemical molecules (Gilbertson lab, U Houston), cell cultures (with Watson lab), and viral-mediated gene manipulations (with Green lab).

Selected Publications

Leggio, G.M., Cathala, A., Moison, A., Cunningham, K.A., Piazza, P.V., and Spampinato, U. Serotonin2C receptors in the medial prefrontal cortex facilitate cocaine-induced dopamine release in the rat nucleus accumbens. Neuropharmacology 56:507-513, 2009.

Nic Dhonnchadha, B.., Fox, R.G., Rice, K.C., and Cunningham, K.A. Blockade of the 5-HT2A receptor suppresses cue-evoked reinstatement in a rat self-administration model. Behavioral Neuroscience 123:382-96, 2009.

Lanfranco, M.F., Seitz, P.K.,Morabito, M.V., Emeson, R.B., Sanders-Bush, E., and Cunningham, K.A. Establishment of an innovative real-time PCR method to measure RNA editing of the serotonin (5-HT) 2C receptor (5-HT2CR). J Neurosci Methods, 179: 247-257, 2009.

Pennock, J.D., Stegall, R. Bubar, M.J., Milligan, G., Cunningham, K.A., and Bourne, N. MDMA increases susceptibility to genital herpes infection. J. Infectious Disease 200: 1247-1250, 2009.

dela Cruz, A.M., Herin, D.V., Grady, J.J., and Cunningham, K.A. Novel data analysis in cocaine conditioned place preference: Development and application. Beh. Pharmacol. 20:720-30, 2009.

Anastasio, M.C.,* Lanfranco, M.F.,* Bubar, M.J., Seitz, P.K., Stutz, S.J., McGinnis, A.G., Watson, C.S., and Cunningham, K.A. Serotonin (5-HT) 5-HT2C receptor (5-HT2CR) protein expression is enriched in synaptosomal and postsynaptic compartments of rat cortex. J. Neurochem. 113:1504-1515, 2010. *Authors contributed equally to this study

Liu, S., Lane, S.D., Schmitz, J.M., Waters, A.J., Cunningham, K.A., and Moeller, F.G. Relationship between attentional bias to cocaine-related stimuli and impulsivity in cocaine-dependent subjects. American J. Drug and Alcohol Abuse 37:117-22, 2011.

Anastasio, N.C., Stoffel, E.C., Fox, R.G., Bubar, M.J., Rice, K.C., Moeller, F.G., and Cunningham, K.A. Serotonin (5-hydroxytryptamine) 5-HT2A receptor: Association with inherent and cocaine-evoked behavioral disinhibition in rats. Behavioral Pharmacology, 22:248-61, 2011.

Cunningham, K.A., Fox, R.G., Anastasio, N.C., Jordan, M.J., Stutz, S.J., Moeller, F.G., Gilbertson, S.R., and Rosenzweig-Lipson, S. Selective serotonin 5-HT2C receptor (5-HT2CR) activation suppresses the reinforcing efficacy of cocaine and sucrose but differentially affects the incentive-salience value of cocaine- vs. sucrose-associated cues. Neuropharmacology 61:513-523, 2011.

Bubar, M.J., Stutz, S.J., and Cunningham, K.A. 5-HT2C Receptors localize to dopamine and GABA neurons in the rat mesoaccumbens pathway. PLoS ONE 6:e20508, 2011.

Liu, S., Lane, S.D., Schmitz, J.M., Green, C.E., Cunningham, K.A., and Moeller, F.G. Increased intra-individual reaction time variability in cocaine-dependent subjects: Role of cocaine-related cues. Addictive Behaviors 37:193-1977, 2011.

Shashack, M.J., Cunningham, K.A., Seitz, P.K., McGinnis, A.G., Smith, T. Watson, C.S., and Gilbertson, S.R. Synthesis and evaluation of dimeric derivatives of 5-HT2A receptor (5-HT2AR) antagonist M-100907. ACS Chemical Neuroscience 2:640644, 2011.

Seitz, P.K., Bremer, N.M., McGinnis, A.G., Cunningham, K.A., and Watson, C.S. Parallel quantitative changes in intracellular calcium and extracellular-regulated kinase activation in CHO cells stably expressing serotonin (5-HT) 5-HT2A and 5-HT2C receptors. BMS Neuroscience, in press.

Nielsen, D.A., Huang, W., Hamon, S.C., Maili, L., Witkin, B.M., Fox, R.G., Cunningham, K.A., and Moeller, F.G., Forced abstinence from cocaine self-administration is associated with epigenetic changes in myelin genes in the corpus callosum: A preliminary study. Submitted.

Anastasio, N.C., McGinnis, A.G., Agarov, A., Smith, T.D., Stutz, S.J., Bremer, N.M., Bubar, M.J. Shavkunov, A., Seitz, P.K., Laezza, F.M., Watson, C.S., Gilbertson, S.R. and Cunningham, K.A. Augmentation of serotonin (5-HT) 5-HT2Creceptor signaling upon peptide disruption of the protein complex made between the 5-HT2CR and protein phosphatase and tensin homologue (PTEN). Submitted.

Seitz, P.K., Shashack, M. J., Smith, T.D., McGinnis, A.G., Bremer, N.M., Cunningham, K.A., and Watson, C.S. Novel bivalent serotonin 5-HT2A receptor (5-HT2AR) antagonists exhibit specificity in receptor binding and functional signaling assays. Submitted.