Behavioral and Pharmacological Neuroscience at Indiana University

Preclinical Neuropsychopharmacology Laboratory

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Drugs of Abuse and Reward Seeking Behavior

Much of our research involves drugs of abuse such as cocaine, alcohol and amphetamine. As we are particularly interested in the neuronal mechanisms of dopamine transmission, multiple lines of research in our lab focus on cocaine and amphetamine derivatives. These drugs increase synaptic dopamine and thus act as indirect dopamine agonists. Analysis of this action at the cellular level can help illuminate the neurophysiological mechanisms underlying the stimulant effect of these drugs as well as the drug craving that develops with repeated use.

These issues can be studied in rats conditioned to respond for drug or natural rewards (e.g., food) in one of several conditioning paradigms. Cellular recording can ellucidate changes in neuronal activity in response to drugs. Furthermore, recording data coupled with behavioral conditioning can track changes that occur in the brain as animals either anticipate a reward, receive a reward, or engage in a conditioned task involving drugs of abuse.

Finally, several members of our lab are working to determine whether dopaminergic drugs (including but not limited to drugs of abuse) have a differential effect in model organism of Huntington's disease. See below for a discussion of this research.

Studies of Degenerative disease

Members of our group utilize genetically engineered mice to study Huntington's disease (HD), a degenerative disorder of the central nervous system. While the exact physiological underpinnings of HD are still not fully understood, the disease has been linked to an expansion of the poly-CAG repeat domain of the huntingtin gene.

Our lab uses two lines of HD mice to study the behavioral and physiological symptoms of this disorder; these are the 140CAG and R6/2 lines. 140CAG mice are a knock-in model and display a more gradual disease progression while R6/2 mice are transgenic for the human huntingtin gene and have a more virulent phenotype. Our studies of HD include studies of behavior and physiology. Studies of the behavioral effects of HD include recording and analysis of free-behaving mice as well as analysis of mice in a variety of behavioral paradigms . We employ electrophysiological recording along with fast-scan cyclic voltammetry to study dysfunctions of the prefrontal cortex, striatum and substantia nigra in HD mice. We also use immunohistochemistry and protein binding to ellucidate molecular changes in the brains of HD animals. Finally, we test dopamine agonists in HD mice in order to determine whether dopaminergic transmission is altered in HD. These hypotheses can be tested by using drug administration in concert with techniques such as voltammetry and single-unit recording.

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