ACTIVATION OF ARC, A PUTATIVE EFFECTOR IMMEDIATE-EARLY GENE, BY COCAINE IN RAT-BRAIN

As immediate early genes (IEGs) are thought to play a critical role in mediating stimulus-induced neuronal plasticity, several laboratories have characterized the IEG response induced by cocaine to help define the changes in gene expression that may underlie its long-lasting beha vioral effects. Although activation of several transcription factor IE Gs has been described, little is known about which ''effector'' IEGs, if any, are also induced. In the present study, we have examined wheth er cocaine administration affects expression of a recently identified ''effector'' IEG, referred to as are (activity-regulated, cytoskeleton -associated). This IEG encodes a protein with homology to spectrin tha t appears to be associated with the actin cytoskeleton. Using in situ hybridization, we have found that systemic cocaine administration elic its a robust, transient rise in are mRNA levels in striatum, which is suppressed by D-1 dopamine receptor blockade, reserpine treatment, or striatal 6-hydroxydopamine tesions. D-2 receptor antagonists triggered are expression when administered alone. Immunohistochemical studies i ndicated that Are protein induced by cocaine is expressed in neuronal cell bodies and dendrites. As Are appears to be a component of the neu ronal cytoskeleton, it may be involved in structural alterations under lying neuronal plasticity triggered by cocaine.