Alcohol and nicotine are commonly co-abused substances. Genetic studies have provided evidence that genes influence the responses to both of these drugs independently, but more recently there have been data to suggest that common gene(s) are likely to influence responses to both drugs. There is an abundant amount of animal research providing evidence that neuronal nicotinic acetylcholine receptors, in particular 1422- containing receptors are involved in the behavioral responses to nicotine. Important for this proposal, these receptors have also been implicated in sensitivity to some effects of alcohol. Nicotinic acetylcholine receptors containing the 14 and 22 subunits have been shown to play a key role in regulating dopamine release in brain regions known to be important for underlying responses to abused drugs. This proposal focuses on the role of natural variation in these receptor subunits in alcohol and nicotine behaviors. Two samples will be used to determine if single nucleotide polymorphisms (SNPs) in the genes encoding these subunits influence sensitivity to alcohol and nicotine phenotypes. DNA and phenotypic data that have already been collected from the Colorado Center for Antisocial Drug Dependence (CADD) and the National Youth Survey (NYS) studies will be available for analysis. The candidate will examine the influence of these genes using resequencing and family-based association tests. Furthermore, the SNPs found to be associated with alcohol or nicotine behaviors will be functionally characterized using luciferase-based gene expression assays. Through this project the candidate will achieve her short-term goal of learning human statistical genetics, molecular genetics and bioinformatics tools. To learn these methods the candidate will attend coursework, symposia, workshops and conferences, in addition to having regular meeting with her mentors. All mentors of this project are faculty fellows at the Institute for Behavioral Genetics. This environment is ideal for such training because of the Institute's long history in studying questions related to the genetics of substance abuse in humans and using animal and molecular approaches. This new training will complement the candidate's prior training in mouse behavioral genetics and will be important for the candidate's long-term goal of becoming an independent researcher. With this additional training in human statistical and molecular genetics the candidate hopes to ultimately evaluate translational questions between model organism and human populations.

Public Health Relevance

Alcohol and nicotine are by far the most commonly co-abused substances and there is evidence that common gene(s) may underlie the response to both drugs. The proposed project will increase our knowledge of the genetic influence the responses to these drugs and may be informative for the development of treatment strategies.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
5K01AA019447-03
Application #
8510526
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Reilly, Matthew
Project Start
2011-08-20
Project End
2016-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$131,859
Indirect Cost
$9,767
Name
University of Colorado at Boulder
Department
Genetics
Type
Other Domestic Higher Education
DUNS #
007431505
City
Boulder
State
CO
Country
United States
Zip Code
80309
Silva, Constanza P; Horton, William J; Caruso, Michael J et al. (2018) The influence of adolescent nicotine exposure on ethanol intake and brain gene expression. PLoS One 13:e0198935
Caruso, M J; Seemiller, L R; Fetherston, T B et al. (2018) Adolescent social stress increases anxiety-like behavior and ethanol consumption in adult male and female C57BL/6J mice. Sci Rep 8:10040
Caruso, M J; Reiss, D E; Caulfield, J I et al. (2018) Adolescent chronic variable social stress influences exploratory behavior and nicotine responses in male, but not female, BALB/cJ mice. Brain Res Bull 138:37-49
Caruso, Michael J; Crowley, Nicole A; Reiss, Dana E et al. (2018) Adolescent Social Stress Increases Anxiety-like Behavior and Alters Synaptic Transmission, Without Influencing Nicotine Responses, in a Sex-Dependent Manner. Neuroscience 373:182-198
Kamens, Helen M; Silva, Constanza; Peck, Colette et al. (2018) Varenicline modulates ethanol and saccharin consumption in adolescent male and female C57BL/6J mice. Brain Res Bull 138:20-25
Caruso, Michael J; Kamens, Helen M; Cavigelli, Sonia A (2017) Exposure to chronic variable social stress during adolescence alters affect-related behaviors and adrenocortical activity in adult male and female inbred mice. Dev Psychobiol 59:679-687
Kamens, Helen M; Peck, Colette; Garrity, Caitlin et al. (2017) ?6?2 nicotinic acetylcholine receptors influence locomotor activity and ethanol consumption. Alcohol 61:43-49
Kamens, Helen M; Silva, Constanza; McCarthy, Riley et al. (2017) No evidence of a role of the ?4 subunit of the nicotinic acetylcholine receptor in alcohol-related behaviors. BMC Res Notes 10:151
Locker, Alicia R; Marks, Michael J; Kamens, Helen M et al. (2016) Exposure to nicotine increases nicotinic acetylcholine receptor density in the reward pathway and binge ethanol consumption in C57BL/6J adolescent female mice. Brain Res Bull 123:13-22
Kamens, Helen M; Corley, Robin P; Richmond, Phillip A et al. (2016) Evidence for Association Between Low Frequency Variants in CHRNA6/CHRNB3 and Antisocial Drug Dependence. Behav Genet 46:693-704

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