Technological advances over the last decade are changing the face of behavioral neuroscience research. Here we review recent work on the use of one such transformative tool in behavioral neuroscience research, chemogenetics (or Designer Receptors Exclusively Activated by Designer Drugs, DREADDS). As transformative technologies such as DREADDs are introduced, applied, and refined, their utility in addressing complex questions about behavior and cognition becomes clear and exciting. In the behavioral neuroscience field, remarkable new findings now regularly appear as a result of the ability to monitor and intervene in neural processes with high anatomical precision as animals behave in complex task environments. As these new tools are applied to behavioral questions, individualized procedures for their use find their way into diverse labs. Thus, “tips of the trade” become important for wide dissemination not only for laboratories that are using the tools but also for those who are interested in incorporating them into their own work. Our aim is to provide an up-to-date perspective on how the DREADD technique is being used for research on learning and memory, decision making, and goal-directed behavior, as well as to provide suggestions and considerations for current and future users based on our collective experience.

This review focuses on the use and application of a powerful new technology, chemogenetics, in behavioral studies. The approach uses synthetically derived receptors and selective ligands for transient activation or inactivation of targeted brain areas, often abbreviated as DREADDs (Designer Receptors Exclusively Activated by Designer Drugs). DREADD receptors can be introduced into neural tissue through a range of gene transfer strategies, allowing for transient and repeatable interventions in brain dynamics upon application of otherwise inert exogenous ligands, for example clozapine-n-oxide (CNO). The rapid expansion of studies using DREADDs has accompanied the development of diverse procedural strategies, both published and transmitted through word-of-mouth. Here we seek to highlight the tremendous potential of the DREADD approach in many behavioral neuroscience research areas—potential that is already being fulfilled in the published behavioral literature—and to provide an overview of considerations in using DREADDs in behavioral studies. We have gathered this material from our experiences; while there remain uncertainties and questions surrounding any new application of DREADD technology, the goal here is to share our own assessment of how the technology can be used effectively for behavioral research. We begin in Section 1 by outlining key advantages of a DREADD-based approach to behavior research compared with traditional or alternative technologies for neural manipulations. In Section 2 we highlight advances in a number of behavioral neuroscience research areas that have emerged by leveraging these advantages, and then discuss in Section 3 various considerations and tips for using and applying DREADD technologies to behavioral neuroscience questions. We conclude in Section 4 with comments on pressing questions for continued DREADD-based research.

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Smith KS, Bucci DJ, Luikart BW, Mahler SV.

Behavioral Neuroscience, Feb 25 , 2016