The objective of the present project is to gain insight into the neurobiological mechanisms underlying the independence producing properties of ethanol and nicotine, and with the knowledge obtained develop new treatment strategies for concomitant alcohol- and nicotine-dependence. More specifically the hypotheses to be tested in the project are the following: 1. Ethanol activates the mesocorticolimbic dopamine system via direct or indirect interference with central nicotinic acetylcholine receptors (nAChR) located a) on dopamine cell-bodies in the ventral tegmental area, and or b) on dopamine neuronal terminals. 2. Subchronic nicotine treatment produces mesocorticolimbical and behavioral sensitization to nicotine and cross-sensitization to ethanol, resulting in enhanced positive reinforcement to ethanol, as investigated in the ethanol drinking preference paradigm. 3. Sensitization to nicotine and ethanol involves activation of transcription factors, e.g. corticosteroids and immediate-early genes. Our research strategy is a top-down analysis. Behaviorally relevant findings (using preference for ethanol in a two choice situation with water) on the individual integrated level is followed down via the system level (where the neurohumoral systems involved are identified and localized in the CNS, using mainly in vivo microdialysis in awake freely moving rats) to the cellular-molecular levels, where the effects of ethanol and nicotine on receptors, signal-transduction systems and transcription factors are studied, using molecular biology methods (RNA-extraction and Northern blots).

Agency
National Institute of Health (NIH)
Institute
National Institute on Drug Abuse (NIDA)
Type
Research Project (R01)
Project #
5R01DA010765-03
Application #
6150445
Study Section
Human Development Research Subcommittee (NIDA)
Program Officer
Aigner, Thomas G
Project Start
1998-05-01
Project End
2001-01-31
Budget Start
2000-02-01
Budget End
2001-01-31
Support Year
3
Fiscal Year
2000
Total Cost
$79,443
Indirect Cost
Name
Goteborg University
Department
Type
DUNS #
City
Gothenburg
State
Country
Sweden
Zip Code
SE-40-530
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