UTMB - The University of Texas Medical Branch

Research Interests

Psychostimulant abuse and addiction [esp., cocaine, substituted amphetamines) remain alarming concerns in society, and new therapeutic directions for prevention and treatment are required. A thorough understanding of the neural basis underlying the effects of these psychoactive drugs is critical to the development of science-based treatment protocols for stimulant overdose and dependence. Serotonin (5-hydroxytryptamine, 5-HT) is involved in the etiology of psychotic (e.g., schizophrenia) and affective disorders (e.g., anxiety, depression) which are often experienced by stimulant abusers. To this end, we have linked human, animal and cellular model systems with target and drug discovery initiatives to achieve breakthrough therapeutic advances for stimulant addiction. The initial theme emerges from clinical evidence linking addiction vulnerability traits (e.g., impulsivity, cue reactivity) to plasticity of serotonin (5-HT) neural systems. Creating a new translational research engine through complimentary, reciprocal, and synergistic interactions among clinical neurobiology, preclinical psychopharmacology, molecular/cellular biology, and drug discovery initiatives we are engaged in three integrated Projects to test the hypothesis that endophenotypic traits (impulsivity, cue reactivity) associated with cocaine dependence emerge from an imbalance in 5-HT function which will be measured at genetic (e.g., 5-HT receptor gene polymorphisms), biological (e.g., 5-HT function in platelets and brain) and systems levels (e.g., response to treatment with 5-HT medications) and that this imbalance can be normalized through selective 5-HT ligands. Working with Scott Gilbertson's group, we are designing new, targeted serotonergic molecules for neurobiology and establishing their promise as new therapeutic modalities for addiction. With the development of this new translational sphere of research activity and the generation of new protocols and paradigms, we will demonstrate that neuronal remodeling in 5-HT systems can lead to behavioral recovery in addiction and jumpstart a new generation of discovery for anti-addiction therapeutics.

Biographical Information

Kathryn A. Cunningham directs a successful research program focused on the role of serotonin neurotransmission in behavior, and is considered one of the world leaders in the role of serotonin in drug abuse and addiction. While some investigators have suggested the potential for new medications based upon selective serotonergic actions, Dr. Cunningham's research has pushed forward this field in understanding the mechanisms of action that will best achieve this end result. Her most recent successes have evolved from her detailed pharmacological and anatomical studies pinpointing the critical roles of the 5-HT2AR and 5-HT2C receptors in the behavioral response to abused drugs. Her studies have uncovered the significance of these proteins not only in the effects of psychostimulants, but also in the function of the reward system in general. Dr. Cunningham is currently employing a cross-disciplinary approach which includes collaborative efforts with medicinal chemists and clinical scientists to develop and test novel compounds that act on these receptors in an effort to new medications for the treatment of psychostimulant dependence. Dr. Cunningham is also active in education and teaches medical and graduate students, residents and other health care professionals in the neurobiology of drug abuse and addiction, serotonin neuropharmacology and pharmacotherapeutics for psychiatric disorders. Author of over 80 research manuscripts, Dr. Cunningham's research has been funded continuously for 19 years by the NIDA, is the Director of a NIDA Center (Translational Center for Serotonin and Stimulant Addiction) and is the recipient of a NIDA Senior Scientist (K05) Award. She is also the Co-Director of a NIDA institutional training grant and has mentored over 20 pre- and post-doctoral students in addiction research. Dr. Cunningham is the Past-President of the College on Problems of Drug Dependence (CPDD) and active member of the CPDD Executive Committee. She also served a 3-year stint on the Board of Directors (2000-2003) and as chairman of the CPDD Publications Committee (1999-2003). Dr. Cunningham serves on NIH study sections (1992-2007), is the Associate Editor of Drug and Alcohol Dependence, and an editorial board member for Neuropsychopharmacology and Behavioral Neuroscience.

Dr. Cunningham received the 2007 ASPET-Astellas Award for Translational Pharmacology and has been the recipient of numerous fellowships and travel awards. She was named the Hedwig van Ameringen designate at the Executive Leadership in Academic Medicine Program for Women in 2000 and honored as the 2001 Distinguished Faculty Research Award at UTMB. She is also active in her community and currently serves on the Board of Directors for the Alcohol and Drug Abuse Women's Program in Galveston, Texas. She lectures on drug abuse, addiction and mental health at community treatment programs and Galveston College and is on the Steering Committee for the Mayor's Roundtable on Drug Abuse, Homelessness and Crime.

Selected Publications

Nic Dhonnchadha, B.A., and Cunningham, K.A. Serotonergic mechanisms in addiction-related memories. Behavioral Brain Research, in press.

Berg, K.A., Clarke, W.P., Cunningham, K.A., Hensler, J.H., and Spampinato, U. Fine-tuning serotonin 5-HT2C receptor function in the brain: Molecular and functional implications. Neuropharmacology, in press.

Bubar MJ, Cunningham KA. Distribution of serotonin 5-HT2C receptors in the ventral tegmental area. Neuroscience. 2007 Apr 25;146(1):286-97. Epub 2007 Mar 23. - Additional Information

Liu S, Bubar MJ, Lanfranco MF, Hillman GR, Cunningham KA. Serotonin2C receptor localization in GABA neurons of the rat medial prefrontal cortex: implications for understanding the neurobiology of addiction. Neuroscience. 2007 Jun 8;146(4):1677-88. - Additional Information

Stoffel EC, Cunningham KA. The relationship between the locomotor response to a novel environment and behavioral disinhibition in rats. Drug Alcohol Depend. 2008 Jan 1;92(1-3):69-78. - Additional Information

Shank EJ, Seitz PK, Bubar MJ, Stutz SJ, Cunningham KA. Selective ablation of GABA neurons in the ventral tegmental area increases spontaneous locomotor activity. Behav Neurosci. 2007 Dec;121(6):1224-33. - Additional Information

Cunningham KA, Watson CS. Cell cycle regulation, neurogenesis, and depression. Proc Natl Acad Sci USA. 2008 Feb 19;105(7):2259-60. - Additional Information

Nic Dhonnchadha BA, Cunningham KA. Serotonergic mechanisms in addiction-related memories. Behav Brain Res. 2008 Dec 16;195(1):39-53. - Additional Information

Sell SL, Craft RM, Seitz PK, Stutz SJ, Cunningham KA, Thomas ML. Estradiol-sertraline synergy in ovariectomized rats. Psychoneuroendocrinology. 2008 Sep:33(8):1051-60. - Additional Information

Bubar MJ, Cunningham KA. Prospects for serotonin 5-HT2R pharmacotherapy in psychostimulant abuse. Prog Brain Res. 2008;172:319-46. - Additional Information

Reilly MT, Cunningham KA, Natarajan A. Protein-protein interactions as therapeutic targets in neuropsychopharmacology. Neuropsychopharmacoloogy. 2009 Jan;34(1):247-8. - Additional Information

Nic Dhonnchadha BA, Fox RG, Stutz SJ, Rice KC, Cunningham KA. Blockade of the serotonin 5-HT2A receptor suppresses cue-evoked reinstatement of cocaine-seeking behavior in a rat self-administration model. Behav Neurosci. 2009 Apr;123(2):382-96. - Additional Information

Lanfranco MF, Seitz PK, Morabito MV, Emeson RB, Sanders-Bush E, Cunningham KA. An innovative real-time PCR method to measure changes in RNA editing of the serotonin 2C receptor (5-HT(2C)R) in brain. J Neurosci Methods. 2009 May 15;179(2):247-57. Epub 2009 Feb 7. - Additional Information

Cunningham KA, Carey AJ, Lycke N, Timms P, Beagley KW. CTA1-DD is an effective adjuvant for targeting anti-chlamydial immunity to the murine genital mucosa. J Reprod Immunol. 2009 Jul;81(1):34-8. - Additional Information

Pennock JW, Stegall R, Bubar MJ, Milligan G, Cunningham KA, Bourne N. 3, 4-Methylenedioxymethamphetamine increases susceptibility to genital herpes simplex virus infection in mice. J Infect Dis. 2009 Oct 15;200(8):1247-50. - Additional Information

Herin, D.V., Seitz, P.K., Thomas, M.L., Hillman, G.R., Tarasenko, Y.I., Wu, P., and Cunningham, K.A. Enhanced vulnerability to the hypermotive effects of cocaine induced by elevated expression of the serotonin 5-HT2A receptor in ventral tegmental area. Submitted.  - Additional Information

Nic Dhonnchadha, B.A., 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. Drug Alcohol Dependence, conditionally accepted. - Additional Information

Stoffel, E.C. and Cunningham, K.A. The relationship between the locomotor response to a novel environment and behavioral disinhibition in rats. Drug Alcohol Dependence. 92:69-78, 2008 - Additional Information

Shank, E.J., Seitz, P.K., Stutz, S.J. and Cunningham K.A. Selective ablation of GABA neurons in the ventral tegmental area increases spontaneous locomotor activity. Behavioral Neuroscience. 121:1224-1233, 2007 - Additional Information

Navailles, S., Moison, D., Cunningham, K.A. and Spampinato, U. Differential regulation of the mesoaccumbens dopamine pathway by serotonin2C receptors in the ventral tegmental area and the nucleus accumbens: an in vivo microdialysis study with cocaine. Neuropsychopharmacology 146:286-297, 2007 - Additional Information

Liu, S., Bubar, M.J., Lanfranco, M.F., Hillman, G.R. and Cunningham, K.A. Serotonin2C receptor localization in GABA neurons of the rat medial prefrontal cortex: Implications for understanding the neurobiology of addiction. Neuroscience 146:1677-1688, 2007 ] - Additional Information

Bubar, M.J. and Cunningham, K.A. Distribution of serotonin 5-HT2C receptors in the ventral tegmental area. Neuroscience 146: 286-297, 2007 [Epub 2007 Mar 23]. - Additional Information

Watson, C.S., Alyea, R.A. Hawkins, B.E., Thomas, M.L., Cunningham, K.A. and Jakubas, A.A. Estradiol effects on the dopamine transporter -- protein levels, subcellular location, and function. J Mol Signal 1:5-18, 2006. - Additional Information

Koldzic-Zivanovic, N., Seitz, P.K., Cunningham, K.A., Thomas, M.L. and T.K. Hughes. Serotonin regulation of serotonin uptake in RN46A cells. Cellular and Molecular Biology, 26:977-985, 2006 - Additional Information

Geng,T., Seitz, P.K., Thomas, M.L., Xu, B., Soman, K.V., Kurosky, A., Luxon, B.A.., and Cunningham, K.A. Use of surface enhanced laser desorption/ionization-time of flight mass spectrometry (SELDI-TOF MS) to study protein expression in a rat model of cocaine withdrawal. J Neurosci Methods 158:1-12, 2006 [Epub 2006 June 9] - Additional Information

Bubar M.J. and Cunningham, K.A. Serotonin 5-HT2A and 5-HT2C Receptors as Targets for Modulation of psychostimulant use and dependence. Curr Top Med Chem 18:1971-1985, 2006. [Review] - Additional Information

Filip, M., Bubar M.J. and Cunningham, K.A. Contribution of serotonin (5-HT) 5-HT2 receptor subtypes to the discriminative stimulus effects of cocaine in rats. Psychopharmacology 183:482-489, 2006 - Additional Information

Bubar, M.J., Seitz, P.K., Thomas, M.L. and Cunningham, K.A. Validation of a selective serotonin 5-HT2C receptor antibody for utilization in fluorescence immunohistochemistry studies. Brain Research, 1063:105-113, 2005 - Additional Information

Liu, S., and Cunningham, K.A. Serotonin2C receptors (5-HT2CR) modulate expression of cocaine-conditioned hyperactivity. Drug and Alcohol Dependence 81:275-282 - Additional Information

Ross, J.D., Herin, D.V., Frankel, P.S., Thomas, M.L., and Cunningham, K.A. Chronic treatment with a serotonin2¬ receptor (5-HT2R) agonist modulates the behavioral and cellular response to (+)-3,4-methylenedioxymethamphetamine [(+)-MDMA]. Drug and Alcohol Dependence, 81:117-127 - Additional Information

Szucs, R.P., Frankel, P.S., McMahon, L.R. and Cunningham, K.A. Relationship of cocaine-induced c-Fos expression to behaviors and the role of serotonin 5-HT2A receptors in cocaine-induced c-Fos expression. Behav. Neurosci., 119:1173-1183, 2005.  - Additional Information

Sell, S.L., Dillon, A.M., Cunningham, K.A. and Thomas, M.L. Estrous cycle influence on individual differences in the response to novelty and cocaine in female rats. Behav. Brain Res. 161:69-74, 2005 [Epub 2005 Feb 3]. - Additional Information

Herin, D.V., Liu, S., Ullrich, T.L., Rice, K.C. and Cunningham, K.A. Role of the serotonin 2A receptor (5-HT2AR) in the hyperlocomotive and hyperthermic effects of (+)-3,4-methylenedioxymethamphetamine. Psychopharmacology 178:505-13, 2005. [Epub 2004 Oct 23]. - Additional Information