Antidepressant Effects of Alcohol and Nicotine

by National Institute of Health

(Page 2 of 6)

Many people use drugs for self-medication of psychological problems, and both alcohol and nicotine have been suggested to have anxiety-reducing (anxiolytic) and antidepressant effects. The use of alcohol for the relief of anxiety, particularly in social situations, was described many years ago in the "tensionreduction" hypothesis. Nicotine has also been said to have anxiolytic properties; however, these properties have been observed primarily in nicotine-dependent people, in whom the drug may act by preventing or relieving the anxietyproducing (anxiogenic) effects caused by nicotine withdrawal.

In animal experiments, researchers have assessed the anxiolytic effects of both alcohol and nicotine using the elevated plus maze test. In that test, rodents are placed in a plus-shaped maze that is elevated above the ground. Of the four arms of the maze, two are open and two are enclosed. The investigators then measure the amount of time the animals spend in the enclosed or open arms of the maze. Because open spaces are a potentially threatening environment for rodents, an increase in the time spent in the open arms after drug administration is thought to reflect an anxiolytic drug action, although this assumption is not entirely uncontroversial. Both alcohol and nicotine have positive effects in this test. Furthermore, these effects may be additive - that is, when alcohol and nicotine are used together, the anxiolytic effect is greater than when either drug is used alone. Other studies, however, have suggested that nicotine has an anxiogenic effect.

The occurrence of both clinical depression and dependence on drugs in the same person (comorbidity) is common, and depression may be a contributing factor in the development of both nicotine dependence and excessive alcohol use. In many cases, however, it is difficult to determine whether pre-existing depression leads to excessive drug use and dependence or whether depression is the result of drug use . Animal experiments that are thought to predict antidepressant properties of drugs have suggested that both alcohol and nicotine may have such an effect. The mechanisms underlying these effects, and whether the combination of alcohol and nicotine has a greater effect than either drug alone, however, have not been thoroughly investigated.

Production of Euphoria and the Rewarding Effects of Alcohol and Nicotine

The term "euphoria" describes the pleasant feeling, or "high," produced by many drugs and is considered a rewarding effect in humans. In animal experiments, where one cannot directly measure emotions such as euphoria, rewarding effects are defined as those drug actions that promote approach behavior.

People commonly report euphoria after drinking alcohol, although the extent depends on the social setting. This effect is frequently given as an important reason for the social use of alcohol. Smokers also have described euphoria from cigarettes. This effect, however, is not necessarily produced in people who do not use nicotine regularly and may be attributable to removal of the unpleasant experience of nicotine withdrawal rather than an intrinsic euphoric action of nicotine.

In animal experiments, rewarding properties of drugs are tested using an experimental design called conditioned place preference, which measures the extent to which a rodent chooses to be in a location where it has previously experienced the effects of a drug. This experimental design has the advantage that the test measurements are made in the absence of the drug; therefore, such drug effects as motor impairment or sedation do not confound the results. However, the procedure normally requires repeated drug administration to produce the association between the place in which the animal is located and the effects of the drug. Consequently, adaptive changes in brain function may occur during this procedure, and the test results may not reflect initial drug effects.

Both alcohol and nicotine have been shown to cause approach behavior to the paired environment in the conditioned place preference test. For nicotine, a complex relationship exists in these studies between the nicotine dose administered and the effects in the test. For alcohol, conditioned place preference has been reported to occur only after longer periods of conditioning than are required for other psychostimulant drugs (amphetamine), and differences among species have been found. Thus, it can be difficult to produce such an effect in rats, whereas an effect can be seen in mice after relatively short conditioning periods. There has been limited investigation of the extent to which the combination of alcohol and nicotine shows additive effects in this test.

Relatively strong evidence indicates that the acute euphoric actions of alcohol contribute to its use in humans, although evidence of this same effect from nicotine is weaker. It will be important for researchers to establish whether using alcohol and nicotine in combination increases the euphoric, and therefore rewarding, actions of these drugs or whether concomitant alcohol drinking may perhaps result in a euphoric effect of nicotine in humans that is not seen when nicotine is used alone.

There has, however, been little experimental investigation of such interactions in humans. In one study, participants reported greater subjective enjoyment of cigarettes during alcohol consumption, although this finding was not reflected in their subsequent preferences for cigarettes that were similar (of the same color) to those they had smoked while under the influence of alcohol. Experimental investigation of nicotine's euphoric effects in humans is complicated both by the need to remove the potentially confounding effects of nicotine withdrawal if tests are conducted on smokers and by the ethical considerations (the strong potential for inducing dependence) of examining the behavioral effects of nicotine in nonsmokers.

Another experimental design thought to be related to rewarding properties of drugs is intracranial self-stimulation. Animals will voluntarily press a lever to receive an electrical stimulation from electrodes implanted in certain brain areas, particularly the hypothalamus and the ventral tegmental area. Conversely, the animals show no apparent interest or even actively avoid stimulation of many other areas of the CNS. Drugs, including both alcohol and nicotine, lower the thresholds for such selfstimulation (the threshold at which such responding is initiated). Schaefer and Michael found additive effects of alcohol and nicotine on selfstimulation of the lateral hypothalamus, but only with one dose combination of the two drugs.

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.