Molecular mechanisms of drug addiction [published erratum appears in J Neurosci 1992 Aug;12(8):following table of contents]

Abstract

Drug addiction has afflicted mankind for centuries, yet the mechanisms by which particular drugs lead to addiction, and the genetic factors that make some individuals particularly vulnerable to addiction, have remained elusive.From a clinical perspective, drug abuse continues to exact enormous human and financial costs on society, yet all currently available treatments for drug addiction are notoriously ineffective.The search for a better understanding of the neurobiological mechanisms underlying the addictive actions of drugs of abuse and of the genetic factors that contribute to addiction should be given a high priority, as this should result in crucial advances in our ability to treat and prevent drug addiction.From the basic neuroscience perspective, study of the neurobiology of drug addiction offers a novei opportunity to establish the biological basis of a complex and clinically relevant behavioral abnormality.Many prominent aspects of drug addiction in people can be clearly reproduced in laboratory animals, in striking contrast to most other forms of neuropsychiatric illness, such as psychotic and affective disorders, animal models for which are much harder to interpret.Advances made in the study of drug addiction should provide important insights into mechanisms underlying some of these other disorders.Three terms related to drug abuse are used commonly: tolerance, dependence, and addiction.Tolerance represents a reduced effect upon repeated exposure to a drug at a constant dose, or the need for an increased dose to maintain the same effect.Dependence is defined as the need for continued exposure to a drug so as to avoid a withdrawal syndrome (physical and/ or psychological disturbances) when the drug is withdrawn.Dependence is considered a priori to result from adaptive changes that develop in body tissues in response to repeated drug exposure.The traditional distinction between physical and psychological dependence is somewhat artificial, since both are mediated by neural mechanisms, possibly even similar neural mechanisms, as will be seen below.Addiction is defined as the compulsive use of a drug despite adverse consequences.