Alcohol and Nicotine

Tolerance and Sensitization After Prolonged Use
by National Institute of Health

(Page 4 of 6)

The effects of alcohol and nicotine on brain neurons and on behavior change when these drugs are taken repeatedly or over long periods. As previously described, the rate of development of dependence on nicotine is faster than that on alcohol, and the neuroadaptive changes need to be evaluated in this context. To what extent tolerance contributes to the development of dependence on alcohol and nicotine is a matter of debate. Tolerance to the unpleasant effects of a drug, which is thought to develop with both alcohol and nicotine, is likely to increase drug use, as described earlier in this article. Tolerance to the pleasant effects of a drug, which develops at least with alcohol, also may result in the drug being taken in larger doses in order to achieve the same effect. Furthermore, cross-tolerance between the behavioral effects of alcohol and nicotine has been seen in experimental studies - that is, animals that develop tolerance to the effects of one drug may also become tolerant to the effects of the other drug but the situation is complex and depends on the measurement and the strain of rodent.

In recent years much attention has been paid to sensitization, which is an increase in the effects of drugs of dependence, including alcohol and nicotine, seen after repeated intake. This sensitization is a long-lasting effect and therefore is a prime candidate for the prolonged nature of dependence. There is considerable uncertainty, however, as to whether sensitization occurs in humans. The "incentive-sensitization" theory of Robinson and Berridge suggested that the "incentive salience" (the importance to an individual) of drugs of dependence and of stimuli associated with the drugs increases as these drugs are taken repeatedly and therefore acquire strong motivating properties and control over behavior.

Animal studies have focused primarily on sensitization to the effects of drugs on locomotor activity. Sensitization to the locomotor stimulant actions of both nicotine and alcohol occurs in experimental animals, although with considerable strain differences in the case of alcohol. Researchers also have reported cross-sensitization between drugs, including those from different pharmacological classifications, such as psychostimulants and opiates. Chronic alcohol consumption was found to increase the locomotor activity following repeated injections of nicotine. If a similar situation existed in humans (if prior alcohol consumption could enhance the effects of nicotine), this would have important implications for the combined use of the two drugs.

Withdrawal Symptoms

The appearance of a withdrawal syndrome after cessation of long-term drug consumption is an important criterion in the diagnosis of dependence and in the definition of a drug's dependence liability. The importance of the withdrawal syndrome in the genesis of dependence, however, is now uncertain. The acute manifestations of withdrawal differ for nicotine and alcohol. Tremor, convulsion, and hallucinations are evident following cessation of long-term alcohol consumption, whereas nicotine withdrawal is associated predominantly with irritability, sleep disturbances, and hunger. There is some similarity, however, in the occurrence of anxiety and unhappiness (dysphoria) in both syndromes. It is still unknown whether simultaneous withdrawal from alcohol and nicotine results in a more severe syndrome than withdrawal from each drug separately. Some laboratory evidence suggests, however, that this may indeed be the case.

The symptoms described above are the subjective feelings seen immediately after withdrawal from chronic intake of the drugs and last a relatively short time after cessation of drug use. The compulsive drug taking, however, lasts far longer, which has led many researchers to discount withdrawal as an important factor in dependence, although addicts often report taking drugs to remove the subjectively unpleasant experience of withdrawal as a major reason to continue drug taking. In addition, treatment of the acute withdrawal symptoms does not prevent dependence on drugs. The importance of withdrawal signs, however, depends on the duration of withdrawal that is considered, and recently attention has been turning to the investigation of behavioral and neurochemical changes that occur or persist at longer times into the abstinence period. Conditioned withdrawal can also occur after considerable duration of abstinence.

The Reinforcing Effects of Alcohol and Nicotine

Reinforcing effects are those actions of drugs that increase the relationship between a stimulus (presentation of an alcoholic beverage) and a response (drinking). In behavioral terms, a reinforcing effect of a drug will promote the behavior that preceded the stimulus. These reinforcing properties of drugs are often confused with, and equated with, the rewarding effects of drugs, which have been discussed earlier. However, the two properties are not identical, and the distinction has been elegantly discussed by White. "Reward" involves feelings of pleasure and therefore describes the hedonic or euphoric effects of drugs, whereas "reinforcement" refers to the relationship between the behavior and the stimulus (in this instance, the drug). Many drugs that cause dependence have both reinforcing and rewarding effects, but the reinforcing actions need not involve pleasant or euphoric effects, and some reinforcing stimuli are actually aversive. Negative reinforcement occurs when the response involves avoidance of the stimulus and is used to describe the situation when a drug is taken to remove the unpleasant effects of drug withdrawal. Reinforcement has been equated with memory and learning; however, whereas nicotine can improve memory and learning, alcohol, over the dose range normally consumed by humans, does not have this action and at high doses is amnesic (causes memory impairment).

About the Author

NIH is the nation's medical research agency - making important medical discoveries that improve health and save lives. The National Institutes of Health (NIH), a part of the U.S. Department of Health and Human Services, is the primary Federal agency for conducting and supporting medical research.