TOLERANCE AND SENSITIZATION TO THE BEHAVIORAL-EFFECTS OF DRUGS

Tolerance and sensitization are relatively simple manifestations of le arning and memory that refer to decreases and increases in the strengt h of a response to a stimulus induced by past experiences with the sam e or related stimuli. In the context of the study of drugs, tolerance refers to the decreased effectiveness of a given drug with repeated ad ministration; sensitization to the increased effectiveness with repeat ed administration. Tolerance usually involves active adjustments or ad aptation to the drug-induced disturbances of function, either within c ells or within a neural system. In situations involving inter-neuronal events, these processes of adjustment may take the form of learned mo difications that can be re-evoked on future occasions by events that c o-occurred at the time of the original modifications. Sensitization, d efined as the enhancement of a directly elicited drug effect, though a daptive, appears to represent facilitation within a system, making the effect easier to elicit on future occasions. Like tolerance, sensitiz ation of a drug effect can become linked to the events that co-occurre d when the effect was originally elicited, making it possible for sens itization to come under selective event control. This paper is concern ed with factors that affect whether tolerance and/or sensitization to the various effects of drugs will develop and be expressed, and with t he variety and levels of mechanisms responsible for tolerance and sens itization under different conditions of exposure.