Effect of nicotine on brain activation during performance of a working memory task

Nicotine influences cognition and behavior, but the mechanisms by which the se effects occur are unclear. By using positron emission tomography, we mea sured cognitive activation (increases in relative regional cerebral blood f low) during a working memory task [2-back task (2BT)] in 11 abstinent smoke rs and 11 ex-smokers. Assays were performed both after administration of pl acebo gum and 4-mg nicotine gum. Performance on the 2BT did not differ betw een groups in either condition, and the pattern of brain activation by the 2BT was consistent with reports in the literature. However, in the placebo condition, activation in ex-smokers predominated in the left hemisphere, wh ereas in smokers, it occurred in the right hemisphere. When nicotine was ad ministered, activation was reduced in smokers but enhanced in ex-smokers. T he lateralization of activation as a function of nicotine dependence sugges ts that chronic exposure to nicotine or withdrawal from nicotine affects co gnitive strategies used to perform the memory task. Furthermore, the lack o f enhancement of activation after nicotine administration in smokers likely reflects tolerance.