The processes of alcohol tolerance and dependence - Special Focus: Alcohol and the Brain

Alcohol Health & Research World, Spring, 1990 by R. Adron Harris, Karl J. Buck

Behavioral Tolerance. Behavioral tolerance, or, more accurately, behaviorally augmented tolerance, develops when a person or laboratory animal learns to function under the influence of a drug. Behavioral tolerance to the incoordinating effects of alcohol h as been demonstrated in rats. In laboratory studies, one group of rats was given alcohol in their cage; another group of rats was given alcohol while performing a motor coordination test. Both groups of animals were then tested on the motor coordination test. Those that received alcohol in their cage developed little tolerance to the incoordinating effects of alcohol. However, those that received alcohol while they were performing the test quickly developed tolerance (Kalant et al. 1971; Wenger et al. 1981).

Tolerance to alcohol is also environmentally dependent; that is, animals that develop tolerance in one environment may not demonstrate tolerance when tested in another environment (Tabakoff and Melchior 1981). This aspect of tolerance raises the interesting possibility that tolerance may, in some ways, be very similar to learning and memory. For both phenomena, the response to a stimulus changes as the stimulus is repeated. It is clear that repeated administration of a drug produces neurochemical changes that change brain function, and that these changes can be long lasting.

The idea that some of the mechanisms responsible for learning and memory also are involved in drug tolerance led to studies with drugs and hormones known to alter memory. For example, the antidiuretic hormone arginine vasopressin appears to enhance long-term memory and also maintains tolerance to alcohol after alcohol consumption has ceased (Hoffman et al. 1978; Tabakoff and Hoffman 1988). Drugs that reduce the action of vasopressin accelerate the loss of tolerance (Tabakoff and Hoffman 1988). Outside the brain, vasopressin decreases excretion of water by the kidneys and increases blood pressure. Pharmacologic agents that mimic the actions of vasopressin in the brain but that lack vasopressin's antidiuretic and blood pressure effects are able to maintain alcohol tolerance. This suggests that therapeutic agents might be used to modify the development or maintenance of alcohol tolerance in humans without producing endocrinological side effects (Tabakoff and Hoffman 1988).

Neuronal Tolerance (Cellular Adaptation). The brain is remarkable for its ability to adapt to the presence of external influences, such as alcohol exposure. Brain cells that have become tolerant to alcohol may function normally when exposed to a concentration of alcohol that initially altered their function. This phenomenon is the subject of active investigation by neurochemists who have focused on various neurotransmitter, receptor, and second messenger systems that might be involved. This topic is discussed in detail in a later section.

ALCOHOL DEPENDENCE

In addition to tolerance, chronic drug intake often results in physical and psychological dependence. The hallmark of physical dependence is that upon discontinuation of drug intake there are clear signs of withdrawal resulting from the absence of the drug in the body. In general, these signs are the opposite of the acute effects of the drug. For example, with sedative drugs such as alcohol, barbiturates, or benzodiazepines, withdrawal results in anxiety, agitation, sleeplessness, and, in extreme cases, seizures (Jaffe 1985).