Influence of Age and Sex on Alcohol Metabolism and Acute Responses

This study will be conducted in social drinkers with no current or past history of alcohol dependence or alcohol abuse. Inclusion criteria include:

1. Male and female participants between 21-25 years or 55-65 years of age.
2. Good health as determined by medical history, physical exam, EKG and lab tests.
3. Current non-smokers. Participants who quit smoking for over 1 year can be included.
4. Family-history negative, i.e., no family history of alcoholism in the first-or second-degree.
5. Young women will have normal menstrual cycles and will be tested during the follicular phase of their cycle (within 7 days of offset of menses) and must have a negative urine pregnancy (hCG) test at the start of each study session.
6. Older women will be post-menopausal, with cessation of menses for at least 12 months prior to enrollment into the study, and a serum follicle stimulating hormone (FSH) level greater than 40 IU/L.
7. All participants must report the absence of flushing either currently or in the past, based on the Alcohol Flushing Questionnaire, assessed during screening.
8. Participants must have no ferromagnetic objects in their bodies which might be adversely affected by MRI (e.g. surgical clips; metal fragments in any part of the body; cardiac or neurological pacemaker; cochlear or eye implant) - any doubt about presence of these objects will result in exclusion from this study.

EXCLUSION CRITERIA:

1. Current or prior history of any disease, including cardiovascular, respiratory, gastrointestinal, hepatic, renal, endocrine, or reproductive disorders, or a positive hepatitis or HIV test at screening.
2. Current history of Axis-I psychiatric illness.
3. Current or prior history of any alcohol or drug dependence or abuse, as well as non-drinkers (alcohol-naive individuals or current abstainers).
4. Alcohol use exceeding 14 drinks/week for males and 7 drinks/week for females, and use of more than 4 drinks on any one occasion in the 6 months prior to the study.
5. Positive result on urine drug screen.
6. Pregnancy or intention to become pregnant for women. Female participants will undergo a urine beta-hCG test to ensure they are not pregnant.
7. Use of oral contraceptive pills in younger female participants and use of hormone replacement therapy in older female participants.
8. Menstrual cycle irregularities in younger female participants.
9. Use of prescription or OTC medications known to interact with alcohol within 2 weeks of the study. These include, but may not be limited to: isosorbide, nitroglycerine, benzodiazepines, warfarin, cough-and-cold preparations which contain anti-histamines, codeine and/or acetaminophen, anti-depressants such as amitriptyline, clomipramine and nefazodone, anti-diabetes medications such as glyburide, metformin and tolbutamide, H2-antagonists for heartburn such as cimetidine and ranitidine, muscle relaxants, pain medicines and anti-inflammatories such as aspirin, ibuprofen, acetaminophen, celecoxib and naproxen, anti-epileptics including phenytoin and phenobarbital and narcotics including darvocet, percocet and hydrocodone. Drugs known to inhibit or induce enzymes that metabolize alcohol should not be used for 4 weeks prior to the study. These include acetaminophen, chlorzoxazone, isoniazid, metronidazole and disulfiram.
10. Exclusions also include herbal preparations containing soy isoflavones (which may have estrogenic properties).
11. Inability to undergo the MRI scan for liver volume due to claustrophobia or anxiety when confined to small spaces such as the magnet bore, or due to the presence of metallic implants.