BEHAVIORAL TOLERANCE

In everyday language, Tolerance implies the ability to withstand something. In pharmacology, the term tolerance is close to this meaning. To understand the technical meaning of the word, however, requires an understanding of the concept of the potency of a drug. A drug's potency is expressed in terms of the amount (the dose) of the drug needed to produce a certain effect. To illustrate, drugs may be compared with respect to potency. For example, relief from headache may be achieved with 650 milligrams of aspirin or with 325 milligrams of ibuprofen; in this case ibuprofen is said to be more potent, because less drug is needed to produce a particular effect (relief of headache). Tolerance is said to occur when a drug becomes less potent as a result of prior exposure to that drug. That is, following exposure (usually repeated or continuous administrations) to a drug, it may take more of the drug to get the same effect as originally produced.

The expression behavioral tolerance often is used simply to refer to a drug's decreased potency in affecting a specified behavior after repeated or continuous exposure to the drug. In other contexts, however, the expression has taken on a more restricted and special meaning; it is employed only when behavioral factors have been shown experimentally to have contributed to the development of tolerance.

This special meaning is applied when either of two sets of circumstances are encountered. In the first, drug tolerance is shown to be specific to the context in which the drug is administered; in the second, drug tolerance is shown to occur only if drug administration precedes particular behavioral circumstances. Examples of each may help clarify the distinctions between them and between "simple" tolerance and behavioral tolerance.

Context-specific tolerance has been researched extensively by Siegel and his colleagues (see Siegel, 1989, for an overview). In a typical experiment two groups of subjects are compared; subjects in both groups receive the same number of repeated exposures to the drug (e.g., morphine) and then are tested for their response to the drug (e.g., alleviation of pain). For one group, the test occurs in the environment where drugging took place; for the other the test occurs in a novel environment. Typically, only those from the group tested in the familiar environment show tolerance. Siegel's theory is that subjects develop, via the principles of Pavlovian conditioning, a conditioned compensatory response that is elicited by the drug-administration context—and that this response counteracts the effect of the drug (see Baker & Tiffany, 1985, for a different view). The phenomenon of context-specific tolerance helps explain why many overdoses of abused drugs occur when the drug is taken in a novel situation—the new context does not elicit compensatory responses that counteract the effects of the drug.

The importance of the temporal relationship between drug administration and behavior is illustrated by the phenomenon of "contingent" tolerance. The basic technique for identifying contingent tolerance was pioneered by Chen (1968), and a clear example is provided by Carlton and Wolgin (1971). Three groups of rats had the opportunity to drink milk for 30 minutes each day. For each group, injections of a drug or just a saline vehicle were made twice each day: For Group 1, each session was preceded by an injection of 2 milligrams per kilogram of Amphetamine, followed by an injection of just the saline vehicle; for Group 2, the order of injections was reversed: saline before drinking, amphetamine after; Group 3 (the control group) received saline both before and after each session.

For Group 1 the drug initially decreased drinking, but during the course of several administrations, drinking recovered to control levels (i.e., tolerance developed). For Group 2, no effect on drinking was observed as a function of receiving the drug after sessions, so after several days (by which time subjects in Group 1 were tolerant) these subjects were given amphetamine before (rather than after) and saline after sessions (i.e., the conditions for Group 1 were implemented). Even though these subjects had received amphetamine just as frequently as the subjects in Group 1, when it was given before the session, drinking was suppressed just as much as it had been for Group 1 initially. Following repeated precession exposure to amphetamine the subjects in Group 2 became tolerant. These findings and many others like them show that, in many cases, for tolerance to develop to a drug's behavioral effects, mere repeated exposure to the drug is not enough. In addition, the drug must be active while the behavior of interest is occurring. (See Goudie & Demellweek, 1986, and Wolgin, 1989, for reviews.)

Contingent tolerance is sometimes called learned tolerance because it appears that it is a manifestation of learning to behave accurately while under the influence of a drug. An influential theory about the origin of contingent tolerance is the "reinforcement loss" theory of Schuster, Dockens and Woods (1966; for a review see Corfield-Sumner & Stolerman, 1978). Loosely stated, the theory is that contingent tolerance will emerge in situations where the initial effect of the drug is to produce a loss of reinforcement (e.g., result in a failure to meet the demands of the task). Although there are limits to the generality of the theory (Genovese, Elsmore, & Witkin, 1988), it has an excellent predictive record.

(See also: Addiction: Concepts and Definitions ; Reinforcement ; Tolerance and Physical Dependence ; Wikler's Pharmacologic Theory of Drug Addiction )

BIBLIOGRAPHY

Baker, T. B., & Tiffany, S. T. (1985). Morphine tolerance as habituation. Psychology Review, 92, 78-108.

Carlton, P. L., & Wolgin, D. L. (1971). Contingent tolerance to the anorexigenic effects of amphetamine. Physiology of Behavior, 7, 221-223.

Chen, C. S. (1968). A study of the alcohol-tolerance effect and an introduction of a new behavioral technique. Psychopharmacologia, 12, 433-440.

Corfield-Sumner, P.K., & Stolerman, I. P. (1978). Behavioral tolerance. In D. E. Blackman & D. J. Sanger (Eds.), Contemporary research in behavioral pharmacology. New York: Plenum.

Genovese, R. F., Elsmore, T. R., & Witkin, J.M. (1988). Environmental influences on the development of tolerance to the effects of physostigmine on schedule-controlled behavior. Psychopharmacology, 96, 462-467.

Goudie, A. J., & Demellweek, C. (1986). Conditioning factors in drug tolerance. In S. R. Goldberg & I. P. Stolerman (Eds.), Behavioral analysis of drug dependence. New York: Academic.

Schuster, C. R., Dockens, W. S., & Woods, J.H. (1966). Behavioral variables affecting the development of amphetamine tolerance. Psycho-pharmacologia, 9, 170-182.

Siegel, S. (1989). Pharmacological conditioning and drug effects. In A. J. Goudie & M. W. Emmett-Oglesby (Eds.), Psychoactive drugs: Tolerance and sensitization. Clifton, NJ: Humana.

Wolgin, D. L. (1989). The role of instrumental learning in behavioral tolerance to drugs. In A. J. Goudie & M. W. Emmett-Oglesby (Eds.), Psychoactive drugs: Tolerance and sensitization. Clifton, NJ: Humana.

Marc N. Branch