Overall, our laboratory is interested in the mechanisms responsible for drug-induced behaviors. We use behavioral and neurochemical techniques to characterize the effects of drugs on behaviors and to understand the mechanisms responsible for these drug effects.
Current Projects
Our laboratory has two ongoing projects.
The goal of our first laboratory project is to determine the effect of lobeline and cannabinoid receptor antagonists on the behavioral and neural pharmacology of psychostimulants and opiates. The long-term goal is the development of a compound to serve as a pharmacotherapy for drug addiction. Recently, our laboratory demonstrated that lobeline (lobelia inflata, a plant native to the southern United States) diminishes cocaine—and morphine—induced hyperactivity and attenuates morphine-evoked dopamine release from brain. Our research with cannabinoid receptors determined that analogs of SR-141716A, a cannabinoid receptor antagonist, alter amphetamine-evoked dopamine release and diminish the locomotor-activating and discriminative-stimulus properties of amphetamine. We have also recently determined that activation and inhibition of cannabinoid receptors diminishes the behavioral, but not the neurochemical, effects of nicotine.
The goal of our second project is to determine the effect of environmental toxicant exposure on the brain and behavior and on pharmacology of drugs of abuse. We recently reported that subchronic cadmium exposure attenuated amphetamine-evoked dopamine release from brain, suggesting that exposure to this “heavy” metal could contribute to drug addiction and psychological disorders such as schizophrenia and Parkinson’s disease. Overall, this research has determined that exposure to relatively-low concentrations of toxicants can produce profound and long-lasting changes in brain function and behavior.
Techniques Used in Our Laboratory
Drug efficacy is assessed in a superfusion assay in which evoked radiolabeled neurotransmitter is measured in brain slices. Locomotor behavior is measured in automated activity monitors. Self-administration and discrimination assays in operant chambers measure the reinforcing and interoceptive properties of drugs, respectively.
Recent Publications
Miller, D. K., Rodvelt, K. R., Constales, C., & Putnam, W. C. (2007). Analogs of SR-141716A (Rimonabant) Alter d-Amphetamine-Evoked [3H] Dopamine Overflow From Preloaded Striatal Slices and Amphetamine-Induced Hyperactivity. Life Sciences, (Accepted).
Dopheide, M. M., Morgan, R. E., Rodvelt, K. R., Schachtman, T. R., & Miller, D. K. (2007). Modafinil Evokes Striatal [3H] Dopamine Release and Alters the Subjective Properties of Stimulants. European Journal of Pharmacology, (In Press).
Miller, D. K., Lever, J. R., Rodvelt, K. R., Baskett, J. A., Will, M. J., & Kracke, G. R. (2007). Lobeline, A Potential Pharmacotherapy for Drug Addiction, Binds to mu Opioid Receptors and Diminishes the Effects of Opioid Receptor Agonists. Drug & Alcohol Dependence, 89(2–3), 282–91.
Rodvelt, K. R., Bumgarner, D. M., Putnam, W. C., & Miller, D. K. (2007). WIN-55, 212–2 and SR-141716A Alter Nicotine-Induced Changes in Locomotor Activity, But Do Not Alter Nicotine-Evoked [3H] Dopamine Release. Life Sciences, 80(4), 337–44.
Polston, J. E., Cunningham, C. S., Rodvelt, K. R. & Miller, D. K. (2006). Lobeline Augments and Inhibits Cocaine-Induced Hyperactivity in Rats. Life Sciences, 79(10), 981–90.
Cunningham, C. S., Polston, J. E., Jany, J. R., Segert, I. L., & Miller, D. K. (2006). Interaction of Lobeline and Nicotinic Receptor Ligands with the Discriminative Stimulus Properties of Cocaine and Amphetamines. Drug & Alcohol Dependence, 84(3), 211–222.
Miller, D. K., Dopheide, M. M., Smith, S. M., & Casteel, S. W. (2005). Dietary Cadmium Exposure Attenuates d-Amphetamine-Evoked [3H] Dopamine Release from Rat Striatal Slices and Methamphetamine-Induced Hyperactivity in Rats. Pharmacology, Biochemistry & Behavior, 80(4), 557–566.
