Intervention: Citalopram
Trial phase: Phase 1
ATC code: N06AB04 | N06AB10
SMILES: CN(C)CCCC1(c2ccc(F)cc2)OCc2cc(C#N)ccc21
Sex: All
Age groups: Adult
Healthy volunteers: Accepts Healthy Volunteers
Participants at risk: 20
Group description: 40 mg citalopram in 250 ml saline infused over 1 hour, in a double-blind, crossover study, with infusion days at least 2 weeks apart.

citalopram: citalopram, 40 mg IV, vs. saline control, each to be administered in a double-blinded, within-subjects design.
Eligibility criteria:
Inclusion Criteria:

Must be U.S. Veteran

Alcohol Dependence:

Age between 21 and 55;
Meeting DSM-IV diagnostic criteria for alcohol dependence;
Report drinking at least 48 standard drinks in a 30-day period, during the 90 days before enrollment, and
Must have had at least 2 days of heavy drinking (at least 5 drinks/day for men, 4 drinks/day for women) in the last 30 days

Healthy Control:

Age between 21 and 55;
No Axis I DSM-IV diagnosis (except for nicotine dependence);
Report drinking less than 10 drinks weekly over the past 90 days prior to study entry by Timeline Followback Method (TLFB).

Exclusion Criteria:

Exclusion criteria for Alcohol Dependence:

Current treatment for alcohol problems or a history of treatment in the 30 days before enrollment or are treatment seeking;
A current (last 12 months) DSM-IV diagnosis of dependence on any psychoactive substances other than alcohol and nicotine.

Exclusion criteria for Healthy Controls:

Any history of treatment for alcohol or other substance use disorders;
Any history of DSM-IV diagnosis of dependence on any psychoactive substances other than nicotine;
Any history of DSM-IV diagnosis of Axis I mental illness.

Exclusion criteria for all subjects:

A current (last 12 months) DSM-IV diagnosis of schizophrenia, bipolar disorder, other psychotic disorder, eating disorder, panic disorder with or without agoraphobia;
Current use of psychoactive drugs, other than occasional marijuana use (< 3 uses per week), as determined by a positive urine screen for narcotics, amphetamines, or sedative hypnotics;
Serious alcohol withdrawal symptoms as indicated by a score > 10 on the Clinical Institute Withdrawal Assessment for Alcohol-Revised (CIWA);
Clinically significant physical abnormalities as indicated by physical examination, hematological laboratory assay, or urinalysis, defined as: hematology and chemistry laboratory tests that are within normal (+/- 10%) limits with the following exceptions: a) liver function tests (total bilirubin, alanine transaminase [ALT], aspartate aminotransferase [AST], and alkaline phosphatase) < 3 x the upper limit of normal, and b) kidney function tests (creatinine and BUN) < 2 x the upper limit of normal;
A screening ECG that demonstrates anything other than normal sinus rhythm, normal conduction, and no clinically significant arrhythmias;
History of epilepsy, seizures, or severe head trauma;
History of alcohol intoxication delirium, alcohol withdrawal delirium or seizure, alcohol-induced persisting dementia, or alcohol-induced psychosis;
Treatment with any of the following medications within the last 30 days prior to randomization: antidepressants, anti-convulsants, hypnotics, antipsychotics, psychomotor stimulants, or anti-anxiety agents;
Previous treatment with citalopram discontinued due to an adverse event;
Pregnancy, nursing, or refusal to use reliable barrier method of birth control, if female;
Presence of metal fragments, pacemaker, or other ferromagnetic material which would prevent safe completion of an MRI scan;
Recent history of radiation exposure which would make exposure to radiation from serial PET scans contraindicated;
Non-zero breath-alcohol level on screening. We will exclude participants who present to study appointments intoxicated, as active alcohol intoxication may interact unpredictably with citalopram and produce unreliable results in assessments of mood or alcohol craving (e.g. Ray and Hutchison, 2007; Ray et al., 2011; see preliminary data C.2. above);
Resting vital signs on any study visit outside of acceptable parameters: Pulse of 50-105 bpm, Blood pressures of 90-160 mm Hg systolic, 55-100 mm Hg diastolic;
Any indication of suicidal ideation (i.e. as assessed by question 9 on the Beck Depression Inventory-II [BDI-II]), or elevated index of depressive symptoms, as evidenced by BDI-II score of 20;
Presence in the body of a metal device (e.g., pacemaker, infusion pump, aneurysm clip, metal prosthesis or plate) that could either interfere with the acquisition of the MRI scan of the brain or for whom the MRI scan would pose a potential risk will be excluded.
Radiation exposure: Participation in any other research study involving exposure to ionizing radiation in the past year if the total cumulative exposure from the past research studies and the current research study would exceed the limits described by the FDA in 21 CFR 361.1. Specifically, the total cumulative dose to the whole body, active blood-forming organs, lens of the eye, and gonads must remain below 5 rems, and the cumulated dose to all other organs must remain below 15 rems over the last year.