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Objective: Controversy exists over the effect of tobacco deprivation in nicotine-dependent individuals and the efficacy of nicotine in reversing performance decrements. This study's aim was to assess the efficacy of nicotine (4-mg lozenge) versus placebo on aspects of cognitive and psychomotor performance, mood, and withdrawal symptoms in male and female established smokers. Methods: Male and female smokers (N = 22; mean age, 28.8 years), with a smoking history of more than 1 year and time to first cigarette of less than 30 minutes upon waking, were enrolled. Baseline measures were obtained at 17 hours of abstinence. At 18-hour abstinence, nicotine or placebo was administered every 2 hours over an 8-hour period. Cognitive and psychomotor performance measurements were taken 30 minutes after dose. Cognitive test battery included Rapid Visual Information Processing, Continuous Tracking Task, Critical Flicker Fusion, Choice Reaction Time, Stroop Test, and Sternberg's Short-term Memory Scanning Task. Withdrawal (Modified Minnesota Withdrawal Scale) and mood (Positive and Negative Affect Schedule) were also assessed. A mixed-models analysis of covariance was performed. Results: Compared with placebo nicotine (4 mg) significantly improved vigilance, divided attention, executive functioning, working memory, and sensorimotor performance in abstinent volunteers (P ≤ 0.05). Withdrawal symptoms including craving, difficulty concentrating, irritability, and restlessness were also attenuated, and affective state was improved after nicotine 4 mg administration. Conclusions: Compared with placebo, nicotine (4 mg) improved measures of vigilance, memory, and attention; improved mood; and reduced withdrawal symptoms. These findings suggest that repeated nicotine replacement therapy over a period of 8 hours can improve cognitive deficits associated with nicotine withdrawal.

The effect of alcohol on aggressive behavior was studied in the highly aggressive transgenic TGF alpha male mouse. In contrast to findings obtained in other aggressive animals, low and moderate doses of alcohol failed to reduce this behavior in the TGF alpha mice; only a high dose reduced aggression. The plasma levels of alcohol were similar in the TGF alpha mice and non-transgenic control mice. However, the loss of righting reflex following an alcohol administration was significantly lengthened in the TGF alpha mice. These results suggest that the male TGF alpha mice can be used to investigate the mechanisms determining the physiological sensitivity to alcohol. Furthermore, these mice represent the first animal model supporting the findings obtained in humans that alcohol maintains pathological aggression.