Effects of nicotine on ethanol dependence and brain damage.

Almost all alcoholics (80%-95%) smoke tobacco. When alcoholics binge, they achieve high, sustained blood alcohol levels, become physically dependent, and often suffer loss of cognition and other higher cortical functions. Nicotine could have a modulatory effect on ethanol drinking behavior and ethanol-induced brain damage through its cholinergic actions. To determine whether nicotine altered alcohol dependence, alcohol-induced brain damage, or both, a rat model of binge drinking was used to study the effects of nicotine on the alcohol withdrawal syndrome and its associated brain damage. After administration of the last dose of ethanol in a 4-day binge model, rats remained intoxicated for approximately 5 h, slowly returned to a neutral state, and entered a hyperexcited period, which peaked around 24 h and lasted a total of 60 h. Behavioral signs of withdrawal included splayed limbs, tremors, and seizures. Continuous transdermal nicotine did not alter the duration or severity of ethanol withdrawal. The 4-day binge ethanol treatment caused considerable brain damage in the perirhinal cortex, entorhinal cortex, ventral dentate gyrus, and olfactory bulb as visualized with amino cupric silver stain. Nicotine alone caused little or no brain damage and did not markedly alter binge ethanol-induced damage in cortical or hippocampal regions. In the olfactory bulb, nicotine reduced ethanol-induced brain damage. Although results of other studies seem to indicate that nicotine increases alcohol consumption, our findings indicate that nicotine does not markedly change the development of alcohol dependence or alcohol-induced cortical damage.