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Neurodegeneration and chronic drug-induced
changes in brain signaling pathways

The focus of this laboratory is on the effects of drugs on synaptic signaling processes with particular interest in the factors involved in neurodegeneration and chronic drug-induced changes in brain chemistry that lead to inappropriate and unhealthy behavior. Recent studies have focused on a process referred to as excitotoxic delayed neuronal death. Excitotoxicity is a process whereby excessive stimulation of neurons, usually by the neurotransmitter glutamate, triggers a delayed neuronal death. NMDA-glutamate receptors and other calcium-conducting ion channels play a key role in excitotoxicity. Excitotoxicity is thought to contribute to the neurodegeneration in patients who have strokes, chronically abuse alcohol, Alzheimer’s disease, Huntington’s disease, brain trauma, and other CNS insults. The hope is that by understanding the basic mechanisms of this process that new therapies will result to treat these disorders.

A second related theme involves the effects chronic drugs have on brain signaling. These processes are involved in the development of tolerance and dependence to drugs of abuse as well as many psychiatric drugs and the environment. We recently discovered that chronic alcohol could increase the sensitivity of neurons to NMDA receptor stimulation resulting in sensitization to excitotoxicity as well as altering signaling processes asssociated with cognitive behaviors. The molecular mechanisms of these changes and how they relate to drug abuse behaviors is an ongoing area of interest.

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