Drug Tolerance

Tolerance is caused due to the ability of brain to adapt to or compensate for the presence of a chemical. The development of tolerance after being repeatedly exposed to a particular drug can be explained through two possible biological processes. One of the processes involves a decline in the concentration of the particular drug at the effector site due to changes in the distribution, excretion, absorption and metabolism of the drug. The second process involves changes in the sensitivity towards a drug due to adaptive changes which diminish the earlier effects of a drug. The nervous system has the ability to adapt and as a result, reduces the earlier effects of a drug through the use of two methods. The first method involves a change in the

The kind of drug tolerance models that has passed from one generation to another, be it emphasises on receptor changes or on altered metabolism, it describes or explains the mechanisms that are underlying tolerance as orgasmic change which results automatically due to the exposure of drugs. Nevertheless, there has been many recent demonstrations of tolerance phenomena which postulates that there is much more to drug tolerance than just drug exposure by itself. At a more specific level, learning and increased knowledge resulting from drug administration may be more inclined to play a significant role in expression, maintenance and expression of drug tolerance (Siegel, 1983). It was noted by Siegel (1975) that any instances when a certain drug is tested or taken can be perceived as a Pavlovian conditioning trial where environmental cues are joined with the effects that is brought about by the drug. Through the process of conditioning, the learning of associating drug effects with surroundings or environments by animals may occur, predictably associated with the administration of drugs. A possibility as such was identified by many researchers previously, however, it was first uncovered by Siegel about the substantial property of the conditioned response which may be drawn from cues that are associated with drugs. It is observed that the response

Drug tolerance may be directly contributed by the compensatory nature of the drug-conditioned response. When the environmental cues and the drug are paired constantly over and over again, the conditioned response that is compensatory drawn by those cues, will tend to grow progressively bigger and would curtail the direct effect of the drug. A view as such is consistent with the demonstrations which morphine analgesic tolerance is precise to the circumstances that form the setting where the drug is administered (Siegel, 1975, 1976, Siegel, Hmson, & Krank, 1978). At a more surprising level, the development of morphine tolerance can be weakened by prior injections of morphine with an explicitly conditioning procedure. These outcomes are predicted in a uniquely manner by a model of conditioning of drug tolerance (Siegel, 1983). Since conditioning is linked with tolerance, an individual would foresee factors which will affect Pavlovian conditioning to have an impact on drug tolerance. There is enough evidence that can be considered from the literature based on morphine tolerance in rats which is consistent with the conditioning model of tolerance. Tolerance to the analgesic effect of morphine may be lessened with processes that are well known to decrease the strength of any other classically