A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder

Andrea L. Dimet; Irma E. Cisneros; Robert G. Fox; Sonja J. Stutz; Noelle C. Anastasio; Kathryn A. Cunningham; Kelly T. Dineley

doi:10.3791/55864

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Method Article

A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder

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DOI:

10.3791/55864

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June 18th, 2018

Andrea L. Dimet^*¹^,²^,³ , Irma E. Cisneros^*¹^,⁴^,⁵ , Robert G. Fox¹^,⁶ , Sonja J. Stutz¹^,⁶ , Noelle C. Anastasio¹^,⁶ , Kathryn A. Cunningham¹^,⁶ , Kelly T. Dineley¹^,³^,⁴

¹Center for Addiction Research, University of Texas Medical Branch, ²Institute for Translational Sciences, University of Texas Medical Branch, ³Mitchell Center for Neurodegenerative Diseases, University of Texas Medical Branch, ⁴Department of Neurology, University of Texas Medical Branch, ⁵Department of Pathology, University of Texas Medical Branch, ⁶Department of Pharmacology and Toxicology, University of Texas Medical Branch

^* These authors contributed equally

Summary

Cue reactivity is conceptualized as sensitivity to cues linked with drug-taking experiences that contribute to craving and relapse in abstinent humans. Cue reactivity is modeled in rats by measuring attentional orientation toward drug-associated cues that results in appetitive approach behavior in a cue reactivity test following self-administration and forced abstinence.

Abstract

Cocaine use disorder (CUD) follows a trajectory of repetitive self-administration during which previously neutral stimuli gain incentive value. Cue reactivity, the sensitivity to cues previously linked with the drug-taking experience, plays a prominent role in human craving during abstinence. Cue reactivity can be assessed as the attentional orientation toward drug-associated cues that is measurable as appetitive approach behavior in both preclinical and human studies. Herein describes an assessment of cue reactivity in rats trained to self-administer cocaine. Cocaine self-administration is paired with the presentation of discrete cues that act as conditioned reinforcers (i.e., house light, stimulus light, infusion pump sounds). Following a period of abstinence, lever presses in the cocaine self-administration context accompanied by the discrete cues previously paired with cocaine infusion are measured as cue reactivity. This model is useful to explore neurobiological mechanisms underlying cue reactivity processes as well as to assess pharmacotherapies to suppress cue reactivity and therefore, modify relapse vulnerability. Advantages of the model include its translational relevance, and its face and predictive validities. The primary limitation of the model is that the cue reactivity task can only be performed infrequently and must only be used in short duration (e.g., 1 hour), otherwise rats will begin to extinguish the pairing of the discrete cues with the cocaine stimulus. The model is extendable to any positively reinforcing stimulus paired with discrete cues; though particularly applicable to drugs of abuse, this model may hold future applications in fields such as obesity, where palatable food rewards can act as positively reinforcing stimuli.

Introduction

Cocaine use disorder (CUD) follows a trajectory of repetitive self-administration during which previously neutral stimuli gain incentive value¹. Cue reactivity is the sensitivity to cues previously linked with the drug-taking experience, and it plays a prominent role in human craving²^,³^,⁴^,⁵. The risk of progression to CUD, as well as relapse during abstinence, is thought to be higher for individuals who express high sensitivity to drug-associated cues⁶^,⁷. Both....