Neural and genetic analyses of motivation and addiction using mice as a model organism. Effects of exercise on the brain and cognition.
My laboratory is broadly interested in exploring how genes and environment affect voluntary behavior. My early work involved a selective breeding experiment in which mice were bred to display extremely high levels of voluntary physical exercise on running wheels. Results of pharmacological studies and brain imaging suggested that the neural basis of high motivation for running shared many features in common with that of motivation to self-administer drugs of abuse. One of the main focuses of my current research program is to study the extent to which the physiological bases of natural forms of motivation (such as motivation for food, sex or exercise) overlap with drug-induced motivation. Current projects include: 1) Using high-resolution brain imaging (immunohistochemical detection of c-Fos and Zif268) to identify brain regions that become activated when mice are placed into an environment where they had previously received a drug of abuse as compared to a natural reward, such as food or sex; 2) Studying the neural and genetic basis of excessive alcohol drinking in mouse models that are genetically predisposed to self administer intoxicating doses of ethanol; 3) Using selective breeding to develop lines of mice that display extremely high levels of physical activity in their home cages to study effects of genetic hyperactivity on learning and memory, aging, stress, responses to drugs of abuse and more generally to identify the genetic basis of hyperactivity and relationship to drug addiction; 4) Studying the effects of exercise on the morphology and physiology of the mouse brain to understand how exercise can improve learning and memory with an emphasis on relating the animal research to current human findings.
Zombeck, J. A., Gupta, T., & Rhodes, J. S. (2009). Evaluation of a pharmacokinetic hypothesis for reduced locomotor stimulation from methamphetamine and cocaine in adolescent versus adult male C57BL/6J mice. Psychopharmacology, 201(4), 589-599.
Clark, P. J., Brzezinska, W. J., Thomas, M. W., Ryzhenko, N. A., Toshkov, S. A., & Rhodes, J. S. (2008). Intact neurogenesis is required for benefits of exercise on spatial memory but not motor performance or contextual fear conditioning in C57BL/6J mice. Neuroscience, 155(4), 1048-1058.
Zombeck, J. A., Chen, G. T., Johnson, Z. V., Rosenberg, D. M., Craig, A. B., & Rhodes, J. S. (2008). Neuroanatomical specificity of conditioned responses to cocaine versus food in mice. Physiology & Behavior, 93(3), 637-650.
Gupta, T., Syed, Y. M., Revis, A. A., Miller, S. A., Martinez, M., Cohn, K. A., et al. (2008). Acute effects of acamprosate and MPEP on ethanol Drinking-in-the-Dark in male C57BL/6J mice. Alcoholism: Clinical & Experimental Research, 32(11), 1992-1998.
Rhodes JS, Ryabinin AE, and Crabbe JC. 2005. Patterns of brain activation associated with contextual conditioning to methamphetamine in mice. Behavioral Neuroscience 119:759-771.
Rhodes JS, Gammie SC, and Garland T, Jr. 2005. Neurobiology of mice selected for high voluntary wheel running activity. Integrative and Comparative Biology 45:438-455.
Rhodes JS, Best K, Belknap JK, Finn DA, and Crabbe JC. 2005. Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice. Physiology and Behavior 84:53-63.
Rhodes JS, and Crabbe JC. 2005. Gene expression induced by drugs of abuse. Current Opinion in Pharmacology 5:26-33.
Bronikowski AM, Rhodes JS, Garland T, Jr, Prolla TA, Awad T, and Gammie SC. 2004. The hippocampal gene expression profile of mice selectively bred for increased voluntary exercise. Evolution 58:2079-2086.