The goal of this research is to better understand the influence of sex-dependent factors on the development of alcoholism. The overarching hypothesis is that there are sex differences in the liability toward alcohol abuse. More specifically, we hypothesize that sex differences partially derive from the effects of gonadal hormones and heritable levels of b-endorphin to influence the neural and behavioral stress response and modify the pleasure derived from alcohol (EtOH) administration.
In Specific Aim 1, we will use mouse models to characterize the role of male versus female gonadal hormones in the effects of stress on EtOH self-administration. Our hypothesis here is that stress will increase the self-administration of EtOH, dependent upon gonadal hormones, such that an ovariectomy of female mice will counter this effect and that castration of male mice will promote it.
Specific Aim 2 will focus on the role of b-endorphin (b-E) and endogenous opioid peptide in the sex-dependent effect of stress on the self-administration of EtOH. As differences in coping behavior and vulnerability to stress have a biological basis in HPA axis function and are modulated by b-E, we will use transgenic mice deficient in the capacity to synthesize b-E to test the hypothesis that behavioral responses contributing to allostasis of the stress response (i.e., EtOH self-administration) will vary as a function of this peptide. Finally, Specific Aim 3 is to employ at lest a dozen undergraduates, including female and underrepresented minority students, to work with the principle investigator on these research projects in a highly mentored environment. As an HHMI Distinguished Mentor with an exemplary record of collaborating with undergraduate students in the laboratory, the PI has a longstanding commitment to the educational benefit that these hands-on skills provide to future neuroscientists.

Public Health Relevance

The goal of this grant application is to better understand the factors that predispose certain people toward excessive alcohol consumption. The overall hypothesis driving this work is that females are more susceptible to the negative-reinforcing effects of alcohol (i.e., moderation of an aversive state) and therefore more likely to find this drug rewarding in or after particularly stressful situations. Males and females have somewhat different factors contributing to addiction, so a better understanding of these influences will promote more effective targeted alcoholic treatment and intervention.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
1R15AA022506-01A1
Application #
8689389
Study Section
Special Emphasis Panel (ZRG1-MDCN-R (86))
Program Officer
Grandison, Lindsey
Project Start
2014-09-05
Project End
2017-08-31
Budget Start
2014-09-05
Budget End
2017-08-31
Support Year
1
Fiscal Year
2014
Total Cost
$360,986
Indirect Cost
$110,986
Name
Bucknell University
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
003030335
City
Lewisburg
State
PA
Country
United States
Zip Code
17837