Investigation of Nicotine Seeking Behavior in Current Smokers

Non-treatment-seeking cigarette smoking individuals were recruited from the Detroit, MI area.
Individuals were screened for cardiovascular, neurological, and psychiatric
contraindications. 21 healthy smokers completed two oral pre-treatment experimental sessions
(on separate non-consecutive days) in randomized order under double-blind conditions: placebo
(lactose) and stress (54mg yohimbine and 10mg hydrocortisone). Yohimbine + hydrocortisone
elicit a neurochemical and physiological response that mimics a 'natural' stressor. Placebo
and stress sessions were identical and started at 11am. Upon arrival, subject sobriety was
confirmed with expired breath alcohol measurement (<.02%). At 11:30am, each subject smoked 6
cigarette puffs (preferred brand; provided by study) over 5 minutes to control for recent
nicotine exposure. Throughout each experimental session, subjects periodically completed
self-reported measures of cigarette craving, nicotine withdrawal symptoms, affect, and
anxiety, and vital signs were measured. Subjects self-administered (swallowed) oral doses of
yohimbine (or placebo) at 11:45am and hydrocortisone (or placebo) at 12:15pm. At 1pm,
subjects completed a 60-min neuroimaging scan which included: 1) T1-weighted structural scan,
2) proton functional magnetic resonance spectroscopy (fMRS) acquisition from the left
prefrontal cortex during a letter 2-back working memory paradigm, and 3) functional magnetic
resonance imaging (fMRI) acquisition during an N-back paradigm yoked with cigarette cues. At
2:30pm, subjects completed an 11-trial choice progressive ratio task in which they could earn
cigarette puffs (preferred brand; provided by study) or money. At 3pm, subjects
self-administered earned cigarette puffs (video monitored). Subjects remained on site until
4pm discharge.

Inclusion Criteria:

- 1) Aged between 21-35 years old, 2) current smokers (expired breath carbon monoxide >
4ppm, self-reported 10+ cigarettes/day, Fagerstrom test for nicotine dependence score
> 3, 3) normal seated and resting vital signs (systolic blood pressure 80-160mmHg,
diastolic blood pressure 50-90mmHg, and heart rate 50-90 bpm), and 4) normal or
corrected-normal vision.

Exclusion Criteria:

- 1) Abnormal electrocardiogram (reviewed by licensed cardiologist), 2) magnetic
resonance imaging contraindications (e.g. metal implants), 3) medical/neurological
contraindications (e.g., diabetes or head trauma), 4) pregnancy (urine test; females
only), 5) positive urine test result for opioids, cocaine metabolites,
benzodiazepines, barbiturates, or amphetamines, 6) psychiatric contraindications
(subject met criteria for current Axis 1 disorder [other than nicotine dependence] as
indicated by computerized MINI-6 screen), and 7) self-reported marijuana and/or
alcohol use on 15+ days in the past month.