Summary

Operante Sensation Seeking in de muis

Published: November 10, 2010
doi:

Summary

In dit protocol beschrijven we een methode voor het operant leren met behulp van zintuiglijke prikkels als een reinforcer in de muis. Het vereist geen voorafgaande opleiding of voedsel beperking, en het laat de studie van gemotiveerd gedrag zonder het gebruik van een farmacologische of natuurlijke bekrachtiger zoals voedsel.

Abstract

Operant methods are powerful behavioral tools for the study of motivated behavior. These ‘self-administration’ methods have been used extensively in drug addiction research due to their high construct validity. Operant studies provide researchers a tool for preclinical investigation of several aspects of the addiction process. For example, mechanisms of acute reinforcement (both drug and non-drug) can be tested using pharmacological or genetic tools to determine the ability of a molecular target to influence self-administration behavior1-6. Additionally, drug or food seeking behaviors can be studied in the absence of the primary reinforcer, and the ability of pharmacological compounds to disrupt this process is a preclinical model for discovery of molecular targets and compounds that may be useful for the treatment of addiction3,7-9. One problem with performing intravenous drug self-administration studies in the mouse is the technical difficulty of maintaining catheter patency. Attrition rates in these experiments are high and can reach 40% or higher10-15. Another general problem with drug self-administration is discerning which pharmacologically-induced effects of the reinforcer produce specific behaviors. For example, measurement of the reinforcing and neurological effects of psychostimulants can be confounded by their psychomotor effects. Operant methods using food reinforcement can avoid these pitfalls, although their utility in studying drug addiction is limited by the fact that some manipulations that alter drug self-administration have a minimal impact on food self-administration. For example, mesolimbic dopamine lesion or knockout of the D1 dopamine receptor reduce cocaine self-administration without having a significant impact on food self-administration 12,16.

Sensory stimuli have been described for their ability to support operant responding as primary reinforcers (i.e. not conditioned reinforcers)17-22. Auditory and visual stimuli are self-administered by several species18,21,23, although surprisingly little is known about the neural mechanisms underlying this reinforcement. The operant sensation seeking (OSS) model is a robust model for obtaining sensory self-administration in the mouse, allowing the study of neural mechanisms important in sensory reinforcement24. An additional advantage of OSS is the ability to screen mutant mice for differences in operant behavior that may be relevant to addiction. We have reported that dopamine D1 receptor knockout mice, previously shown to be deficient in psychostimulant self-administration, also fail to acquire OSS24. This is a unique finding in that these mice are capable of learning an operant task when food is used as a reinforcer. While operant studies using food reinforcement can be useful in the study of general motivated behavior and the mechanisms underlying food reinforcement, as mentioned above, these studies are limited in their application to studying molecular mechanisms of drug addiction. Thus, there may be similar neural substrates mediating sensory and psychostimulant reinforcement that are distinct from food reinforcement, which would make OSS a particularly attractive model for the study of drug addiction processes. The degree of overlap between other molecular targets of OSS and drug reinforcers is unclear, but is a topic that we are currently pursuing. While some aspects of addiction such as resistance to extinction may be observed with OSS, we have found that escalation 25 is not observed in this model24. Interestingly, escalation of intake and some other aspects of addiction are observed with self-administration of sucrose26. Thus, when non-drug operant procedures are desired to study addiction-related processes, food or sensory reinforcers can be chosen to best fit the particular question being asked.

In conclusion, both food self-administration and OSS in the mouse have the advantage of not requiring an intravenous catheter, which allows a higher throughput means to study the effects of pharmacological or genetic manipulation of neural targets involved in motivation. While operant testing using food as a reinforcer is particularly useful in the study of the regulation of food intake, OSS is particularly apt for studying reinforcement mechanisms of sensory stimuli and may have broad applicability to novelty seeking and addiction.

Protocol

1. Schrijf programma om operante testsessies uitgevoerd met gebruikmaking van gevarieerde visuele en auditieve stimuli als een reinforcer Voor vaste ratio (FR) sessies: maak sessies een uur lang met een huis licht en de ventilator ingeschakeld tijdens de sessie. Voor progressieve verhouding sessies maken sessies twee uur in de lengte. Hebben beide hendels verlengd voor de duur van de sessie en tegenwicht die hefboom is "actief" versus "inactief" aangewezen over dieren (hefboom opdracht voo…

Discussion

Operante sensatie zoeken is een bruikbaar alternatief voor de intraveneuze drugs zelfbestuur als de muis is het dier van uw keuze. Het feit dat noch de operatie, noch katheter onderhoud nodig is, is voordelig, omdat deze van belang zijn technische obstakels in de muis. OSS is ook aantrekkelijk, omdat het kan zijn het meten van aspecten van de wapening onderscheidt zich van andere natuurlijke bekrachtigers zoals voedsel.

Het is nuttig op te merken dat gedragsmatige maatregelen in de muis kan …

Divulgazioni

The authors have nothing to disclose.

Acknowledgements

Dit project werd ondersteund door NIH subsidie ​​DA19112 (DGW) en DA026994 (CMO). Illustratie werd geleverd door Katherine Louderback. Experimenten werden uitgevoerd in de Vanderbilt Murine Neurobehavioral Laboratory.

Materials

Material Name Tipo Company Catalogue Number Comment
Drug self-administration test package for mouse: extra-wide chamber and retractable levers   Med Associates, Inc MED-307W-CT-D1 Levers are ultra-sensitive (require ~2 grams force) and are mounted 2.2 cm above the floor. Yellow stimulus lamps are mounted 2 cm above each lever.
Interface and software package   Med Associates, Inc MED-SYST-16 This is the package for up to 16 chambers.

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Citazione di questo articolo
Olsen, C. M., Winder, D. G. Operant Sensation Seeking in the Mouse. J. Vis. Exp. (45), e2292, doi:10.3791/2292 (2010).

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