Tolerance and Physical Dependence
Tolerance and physical dependence are complex biological responses to the chronic administration of drugs and are probably intimately related to basic neurophysiological processes such as habituation and accomodation. Chemical stimuli and receptive mechanisms were probably among the first sensory mechanisms to evolve to assist in satisfying food needs and in avoiding toxic chemicals. To facilitate acquisitive and avoidance movements, negative feedback mechanisms probably developed at a very early stage of evolution. Further, a large portion, perhaps all, of the communication between neurons in the central nervous system is conducted using chemical (neurotransmitters, modulators, and hormones) stimuli and receptors. Finally, virtually all drugs that induce tolerance and dependence exert their actions, either directly or indirectly, by altering neurotransmitter-receptor interactions (Table 1).
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