Activation of an effector immediate-early gene arc by methamphetamine

As immediate-early genes (IEGs) are thought to play a critical role in mediating stimulus-induced neural plasticity, IEG response induced by methamphetamine (METH) has been characterized to define the changes in gene expression that may underlie its long-lasting behavioral effects. Although activation of several transcription factor IEGs has been described, little is known about effector IEGs. Here, we have examined whether METH administration affects expression of an effector IEG arc (activity-regulated, cytoskeleton-associated) that encodes a protein with homology to spectrin. Using in situ hybridization, we observed that METH caused a rapid and transient dose-dependent increase in arc mRNA level in the striatum and cortex that was abolished by pretreatment with the specific dopamine D1 receptor antagonist SCH-23390 but not by an atypical neuroleptic clozapine. METH induced arc mRNA in layers IV and VI of the cortex which dopamine receptor are localized to. These results suggest that D1 receptors are coupled to activation of arc gene, which may be involved in functional or structural alterations underlying neural plasticity triggered by METH.