The study procedure has been described in detail elsewhere.26, 27 Briefly, experimental sessions were conducted the morning (0800) after an overnight abstinence from smoking that was confirmed biochemically. All laboratory subjects had expired carbon monoxide levels less than 10 parts per million and plasma nicotine levels less than 4 ng/ml, indicating abstinence from smoking. After intravenous (IV) lines were established, at baseline, subjects completed the Minnesota Nicotine Withdrawal Scale (MNWS),29 the Positive and Negative Affect Schedule (PANAS),30 and the Brief Questionnaire of Smoking Urges (BQSU).31 They then were administered an IV dose of saline, followed by two doses of IV nicotine per 70 kg of body weight: a moderate dose (0.5 mg) and a high dose (1 mg) in uniform order, separated by 30 minutes. During the experimental session, blood pressure and heart rate were monitored and the effects of nicotine were assessed with the Drug Effects Questionnaire (DEQ). Approximately 20 minutes after the final dose of nicotine, subjects repeated the MNWS, PANAS and BQSU assessments. Institutional review boards at Yale University and VA Connecticut Healthcare System (West Haven, CT) approved the study, written consent was provided before participating in the study, and subjects were paid for their participation.
