DRUGS OF ABUSE AND IMMEDIATE-EARLY GENES IN THE FOREBRAIN

A diverse array of chemical agents have been self administered by huma ns to alter the psychological state. Such drugs of abuse include both stimulants and depressants of the central nervous system. However, som e commonalties must underlie the neurobiological actions of these drug s, since the desire to take the drugs often crosses from one drug to a nother. Studies have emphasized a role of the ventral striatum, especi ally the nucleus accumbens, in the actions of all drugs of abuse, alth ough more recent studies have implicated larger regions of the forebra in. Induction of immediate-early genes has been studied extensively as a marker for activation of neurons in the central nervous system. In this review, we survey the literature reporting activation of immediat e-early gene expression in the forebrain, in response to administratio n of drugs of abuse. All drugs of abuse activate immediate-early gene expression in the striatum, although each drug induces a particular ne uroanatomical signature of activation. Most drugs of abuse activate im mediate-early gene expression in several additional forebrain regions, including portions of the extended amygdala, cerebral cortex, lateral septum, and midline/intralaminar thalamic nuclei, although regional v ariations are found depending on the particular drug administered. Com mon neuropharmacological mechanisms responsible for activation of imme diate-early gene expression in the forebrain involve dopaminergic and glutamatergic systems. Speculations on the biological significance and clinical relevance of immediate-early gene expression in response to drugs of abuse are presented.