Striatal Cell-Type Specific Plasticity in Addiction

Abstract

Abstract The striatum plays a critical role in addiction. Striatal dopamine receptor 1 and 2 (D1 and D2) expressing medium spiny neurons (MSNs) have functionally distinct output circuits through the basal ganglia network to control behavior. Drugs of abuse enhance mesencephalic dopamine release onto MSNs, which drives MSN plasticity and activity leading to addictive behaviors. Consistent with their differential projections in the basal ganglia, D1- and D2-MSNs have different roles in drug-related behaviors and exhibit differential plasticity adaptations following drug intake. Here, we review and compare how psychostimulants, opiates, and alcohol alter synaptic plasticity on both MSN subtypes via glutamatergic and dopaminergic inputs. In addition, we examine molecular adaptations in MSN subtypes including signaling pathways, transcriptional mechanisms, immediate early genes, and chromatin modifications elicited by these three classes of drugs. This chapter provides a detailed description of the striatal MSN subtype-specific studies, which are crucial to understand the complex neurobiological adaptations underlying addiction.