Neural Circuit Plasticity in Addiction

Abstract Addiction is a progressive disorder that involves a transition from social use into a compulsive relapsing state. This behavioral transition reflects a combination of transient and enduring neural adaptations within specific neural circuits that can leave individuals vulnerable to relapse—even following prolonged periods of abstaining from drug use. Commonalities in the ability of abused drugs to promote similar changes in neurochemistry, neurophysiology, and behavior have pushed for a unified theory of substance abuse. While distinctions in how certain drug classes alter the brain certainly exist, emerging evidence regarding drug-induced neural plasticity suggests that modifications in cell signaling produced by different drugs may overlap more than previously believed. This chapter will focus on adaptations in synaptic plasticity within three key substrates of the brains reward circuit—the ventral tegmental area (VTA), prefrontal cortex (PFC), and nucleus accumbens (NAc). We will overview how acute and repeated drug exposure, as well as the temporal effects of withdrawal, alter excitatory and inhibitory signaling in these regions, and when possible, focus on pathway and cell-based neural adaptations and their relevance to addiction behavior.