Alcohol dependence, or "alcoholism", affects approximately 14 million Americans. Currently, only three pharmacotherapies (disulfiram, naltrexone, and acamprosate) have been approved for the treatment of alcohol dependence and these medications are, at best, moderately successful. Thus, there is a great need for the examination of other biological systems, which contribute/influence the drug reward/addiction pathways within the brain, such that the discovery of new targets and new pharmacotherapies will be possible. Other biological systems in addition to dopamine, such as serotonin, and norepinephrine (NE) are thought to be important in several aspects of addiction, including reward, craving and depression. This study will examine the effects of a 5 day course of atomoxetine (a selective NE transporter (NET) inhibitor) (80 mg/day; Strattera or placebo) on alcohol-elicited craving and sensitivity to alcohol. The novelty of this study is that of atomoxetine and the fact that it targets NET, neither of which has heretofore been examined in the context of alcohol dependence. It is hopeful that this study, of 64 total individuals, will provide the PI with sufficient preliminary data to submit a subsequent R01 application to study atomoxetine and the involvement of specific single nucleotide polymorphisms within the NET gene on alcohol-related phenotypes in alcohol dependent and non-dependent populations. The long-term objective of this research is to develop more efficacious treatment interventions for alcohol abuse and dependence.
Name: Placebo ComparatorDescription: 16 NET SNP rs 11648486 CC and CT individuals will receive placebo and then after one week washout period, receive atomoxetine. Medications will be given as 2 capsules 1x day for 5 days; active atomoxetine groups will receive 40 mg for 3 days, followed by 80 or 120mg (.91-1.4 mg/kg) on days 4 and 5Type: Drug
Name: Active Comparator: Atomoxetine, PlaceboDescription: 16 NET SNP rs 11648486 CC and CT individuals will receive atomoxetine and then after one week washout period, receive placebo.Medications will be given as 2 capsules 1x day for 5 days; active atomoxetine groups will receive 40 mg for 3 days, followed by 80 or 120mg (.91-1.4 mg/kg) on days 4 and 5.Type: Drug
Description: This questionnaire is used to assess craving. The AUQ consists of eight items related to urge drink that are rated on a 7-point Likert scale with the extremes anchored by "Strongly Disagree" and "Strongly Agree." The AUQ has demonstrated internal consistency and reliability (Bohn et al., 1995).Measure: Alcohol urge questionnaire Time: On day 5 of medication
There is one SNP
- tachycardia - seizure disorder - prior history of myocardial infarction - Clinically significant cardiovascular disease that precludes safe participation - hepatic or renal impairment; (ie: liver or kidney enzymes > 3x normal limits) - pregnant - currently using MAO inhibitors within 14 days - narrow angle glaucoma - currently taking antidepressants or have taken within the last month - currently taking pressor agents such as: - Alprenolol - Carteolol - Levobunolol - Mepindolol - Metipranolol - Nadolol - Oxprenolol - Penbutolol - Pindolol - Propranolol - Sotalol - Timolol - Acebutolol - Atenolol - Betaxolol - Bisoprolol - Esmolol - Metoprolol - Nebivolol - Carvedilol - Celiprolol - Labetalol - Butaxamine Alcohol-induced Cue-craving Alcohol Sensitivity Hypersensitivity Design: NET genotype groups for rs11648486 SNP (CC 61%; CT 33%; TT 4%) (e.g., C/C and C/T) will be compared to one another in a 2 (NET Genotype: C/C vs. C/T & T/T) x 2 (Medication: atomoxetine 80 mg/day (~ vs. placebo) x 3 (Drink: Drink 1, 2, and 3) mixed factorial repeated measures design using PROC MIXED in SAS by calculating difference scores.