Using DREADDs to investigate addiction behaviors

•DREADDs provide temporal, spatial, and cell-type specific modulation of cellular signaling.•DREADDs alter cell activity in subtle yet complex ways.•DREADDs are uncovering the roles of cells and circuits to drug-induced changes in brain function.•DREADDs may serve as a model for novel therapies that selectively target drug-induced plasticity.

Drug addiction is characterized by compulsive drug-seeking and drug-taking, and a high propensity for relapse. Although the brain regions involved in regulating addiction processes have long been identified, the ways in which individual cell types govern addiction behaviors remain elusive. New technologies for modulating the activity of defined cell types have recently emerged that are allowing us to address these important questions. Here, we review how one such technology, DREADDs (Designer Receptors Exclusively Activated by Designer Drugs), can be used to refine our knowledge of addiction circuitry. These engineered receptors modulate cellular activity by acting on G protein coupled signaling cascades and in this review we pay particular attention to how this slower-onset modulation preferentially regulates behaviors that develop over time.