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Modeling sleep disturbance during nicotine withdrawal

Institution: SRI International
Investigator(s): Teresa Steininger, Ph.D.
Award Cycle: 2002 (Cycle 11) Grant #: 11KT-0218 Award: $424,344
Subject Area: Nicotine Dependence
Award Type: New Investigator Awards

Initial Award Abstract
The goal of our proposed research is to investigate changes in sleep due to nicotine withdrawal in an animal model. Insomnia and frequent awakening from sleep are common side effects of tobacco withdrawal, which can also affect mood and daytime sleepiness. Since insomnia and other withdrawal symptoms are distressing and disabling, they make it harder to stop smoking and contribute to the continuation of smoking. Sleep disturbance is likely due to the effects of nicotine, the active component in cigarette smoke, on brain chemical (neurotransmitter) pathways that normally regulate the sleep-wake cycle. The goal of our proposed research is to establish sleep recording during nicotine dependence and withdrawal. We will optimize the nicotine delivery method and determine the proper dose of nicotine and time of nicotine delivery in order to show measurable and reliable sleep disruption during nicotine withdrawal in the rat.

This model can then be used to test drugs that may be used to treat nicotine withdrawal symptoms. For example, we will use our model to test the effects of the smoking cessation aid Zyban® (bupropion) on sleep. Bupropion is a mild antidepressant used to treat nicotine craving and nicotine withdrawal symptoms such as depression and irritability. Unfortunately, insomnia is a major side effect in some people taking this drug. Therefore, we may see the animal equivalent of insomnia during bupropion delivery in our model.

The final aim of our proposed project is to look for changes due to nicotine delivery or nicotine withdrawal in two of the major neurotransmitter systems involved in the control of the sleep-wake cycle. If we find that they are altered, they may be good candidates for drug treatment in order to decrease the insomnia and sleep disruption seen in nicotine withdrawal. By helping to alleviate withdrawal symptoms, our development of the proposed model will help to increase smoking cessation (or cessation of other tobacco use) and thereby decrease tobacco- and smoking-related heath problems.

The effects of nicotine withdrawal on sleep in the rat
Periodical: Associated Professional Sleep Society Index Medicus:
Authors: Steininger TL, Shew K, Flores J, Kilduff T ABS
Yr: 2004 Vol: Nbr: Abs: Pg:

Sleep disruption during nicotine infusion and withdrawal
Periodical: Society for Neuroscience Abstracts Index Medicus:
Authors: Steininger TL, Flores J, Shew K, Kilduff TS ABS
Yr: 2004 Vol: Nbr: Abs: Pg: