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Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation

Abstract

It has become increasingly important to assess mood states in laboratory animals. Tests that reflect reward, reduced ability to experience reward (anhedonia) and aversion (dysphoria) are in high demand because many psychiatric conditions that are currently intractable in humans (e.g., major depression, bipolar disorder, addiction) are characterized by dysregulated motivation. Intracranial self-stimulation (ICSS) can be utilized in rodents (rats, mice) to understand how pharmacological or molecular manipulations affect the function of brain reward systems. Although many different methodologies are possible, we will describe in this protocol the use of medial forebrain bundle (MFB) stimulation together with the 'curve-shift' variant of analysis. This combination is particularly powerful because it produces a highly reliable behavioral output that enables clear distinctions between the treatment effects on motivation and the treatment effects on the capability to perform the task.

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Figure 1: Key elements of the operant chamber setup.
Figure 2: The 'curve-shift' variant of intracranial self-stimulation (ICSS).
Figure 3: Data collation and analyses.

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Acknowledgements

The authors were supported in part by grants from the National Institutes of Health (DA012736 and MH063266 to W.A.C.; DA023094 to E.H.C.) while writing this protocol.

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Correspondence to William A Carlezon Jr.

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Competing interests

WAC discloses that his group received financial compensation (an individual registration for the Society for Neuroscience conference) from a manufacturer of ICSS equipment (Med Associates) in exchange for a description of technical procedures for its website. WAC is also a member of the scientific advisory board for a company (Myneurolab.com) that sells products described in this protocol.

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Carlezon, W., Chartoff, E. Intracranial self-stimulation (ICSS) in rodents to study the neurobiology of motivation. Nat Protoc 2, 2987–2995 (2007). https://doi.org/10.1038/nprot.2007.441

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