The long-term goals of this research project are to elucidate the molecular and cellular mechanisms for neuroadaptation to ethanol. Different groups of adult Drosophila will be given acute treatment with ethanol, chronic treatment, or will be withdrawn from chronic treatment. These groups will be studied in a battery of tests that measure innate and learned behaviors to gain an appreciation for the scope of behavioral neuroadaptations that occur and to quantify behavioral tolerance, sensitivity, and dependency for ethanol. Microarray analysis of the complete genome of the fly will be used to examine the changes in gene expression that occur in the brain with the ethanol treatments. RNA in situ hybridization and other techniques will be used to verify the microarray expression results and to reveal the spatial expression pattern of the ethanol-regulated genes in the brain. The morphology of some brain neurons, including mushroom body neurons, will be studied using immunohistochemistry, clonal analysis, and electron microscopy to detect and characterize the changes in cellular morphology that occur with ethanol treatment. These studies comprise a comprehensive plan to better understand the behavioral adaptations that occur with ethanol treatment and to reveal the molecular and anatomical correlates of these adaptations.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA013476-05
Application #
6945941
Study Section
Special Emphasis Panel (ZAA1-DD (20))
Program Officer
Neuhold, Lisa
Project Start
2001-09-27
Project End
2006-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
5
Fiscal Year
2005
Total Cost
$253,239
Indirect Cost
Name
Baylor College of Medicine
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
051113330
City
Houston
State
TX
Country
United States
Zip Code
77030
Nieto, Steven J; Quave, Cana B; Kosten, Therese A (2018) Naltrexone alters alcohol self-administration behaviors and hypothalamic-pituitary-adrenal axis activity in a sex-dependent manner in rats. Pharmacol Biochem Behav 167:50-59
Nieto, Steven J; Kosten, Therese A (2017) Female Sprague-Dawley rats display greater appetitive and consummatory responses to alcohol. Behav Brain Res 327:155-161
Haile, Colin N; Kosten, Therese A (2017) The peroxisome proliferator-activated receptor alpha agonist fenofibrate attenuates alcohol self-administration in rats. Neuropharmacology 116:364-370
Ohia-Nwoko, O; Kosten, T A; Haile, C N (2016) Animal Models and the Development of Vaccines to Treat Substance Use Disorders. Int Rev Neurobiol 126:263-91
Nieto, Steven J; Patriquin, Michelle A; Nielsen, David A et al. (2016) Don't worry; be informed about the epigenetics of anxiety. Pharmacol Biochem Behav 146-147:60-72
Gomez, Juan L; Cunningham, Christopher L; Finn, Deborah A et al. (2015) Differential effects of ghrelin antagonists on alcohol drinking and reinforcement in mouse and rat models of alcohol dependence. Neuropharmacology 97:182-93
Kosten, Therese A; Meisch, Richard A (2013) Predicting extinction and reinstatement of alcohol and sucrose self-administration in outbred rats. Exp Clin Psychopharmacol 21:245-51
Reilly, Matthew T; Faulkner, Geoffrey J; Dubnau, Joshua et al. (2013) The role of transposable elements in health and diseases of the central nervous system. J Neurosci 33:17577-86
Ponomarev, Igor; Wang, Shi; Zhang, Lingling et al. (2012) Gene coexpression networks in human brain identify epigenetic modifications in alcohol dependence. J Neurosci 32:1884-97
Kosten, Therese A (2011) Pharmacologically targeting the P2rx4 gene on maintenance and reinstatement of alcohol self-administration in rats. Pharmacol Biochem Behav 98:533-8

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