AMPHETAMINE REGULATES GENE-EXPRESSION IN RAT STRIATUM VIA TRANSCRIPTION FACTOR CREB

Amphetamine is a psychostimulant drug of abuse that can produce long-l ived changes in behavior including sensitization and dependence. The n eural substrates of these drug effects remain unknown, but based on th eir prolonged time course, we hypothesize that they involve drug-induc ed alterations in gene expression. It has recently been demonstrated t hat amphetamine regulates the expression of several genes, including c -fos, via dopamine D1 receptors in rat striatum. Here we report that a mphetamine induces phosphorylation of transcription factor cAMP respon se element binding protein (CREB) in rat striatum in vivo and that dop amine D1 receptor stimulation induces phosphorylation of CREB within s pecific complexes bound to cAMP regulatory elements. In addition, we s how by antisense injection that CREB is necessary for c-fos induction by amphetamine in vivo. Since CREB has been implicated in the activati on of a number of immediate-early genes as well as several neuropeptid e genes, CREB phosphorylation may be an important early nuclear event mediating long-term consequences of amphetamine administration.