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Behav Pharmacol. 1993;4(4):289-312.

Tolerance and sensitization to the behavioral effects of drugs.

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Center for Studies in Behavioral Neurobiology, Department of Psychology, Concordia University, 1455 de Maisonneuve Blvd., Montreal, Quebec, Canada, H3G 1M8.


Tolerance and sensitization are relatively simple manifestations of learning and memory that refer to decreases and increases in the strength of a response to a stimulus induced by past experiences with the same or related stimuli. In the context of the study of drugs, tolerance refers to the decreased effectiveness of a given drug with repeated administration; sensitization to the increased effectiveness with repeated administration. Tolerance usually involves active adjustments or adaptation to the drug-induce disturbances of function, either within cells or within a neural system. In situations involving inter-neuronal events, these processes of adjustment may take the form of learned modifications that can be re-evoked on future occasions by events that co-occurred at the time of the original modifications. Sensitization, defined as the enhancement of a directly elicited drug effect, though adaptive, appears to represent facilitation within a system, making the effect easier to elicit on future occasions. Like tolerance, sensitization of a drug effect can become linked to the events that co-occurred when the effect was originally elicited, making it possible for sensitization to come under selective event control. This paper is concerned with factors that affect whether tolerance and/or sensitization to the various effects of drugs will develop and be expressed, and with the variety and levels of mechanisms responsible for tolerance and sensitization under different conditions of exposure.


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