Name: operant sensation seeking in the mouse
Uploaded: 2010-11-10T11:00:00
Description: Watch this Scientific Journal Video about Operant Sensation Seeking in the Mouse at JoVE.com

Este proyecto fue apoyado por el NIH subvenciones DA19112 (DGW) y DA026994 (OCM). Ilustración fue proporcionada por Katherine Louderback. Los experimentos se realizaron en el Laboratorio de Vanderbilt Neurocomportamentales murino.

1. Escribir un programa para ejecutar sesiones operante prueba utilizando una variedad de estímulos visuales y auditivos como un refuerzo <ol><li> Por relación fija (FR) sesiones: hacer sesiones de una hora de duración con la luz y el ventilador de la casa encendida durante la sesión. Para las sesiones de relación progresiva, hacer sesiones de dos horas de duración. Tiene dos palancas de prorrogarse durante la duración de la sesión y contrapeso que la palanca se denomina &quot;activa&quot; frente a &quot;inact...

<ol>
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R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cue+dependency+of+nicotine+self-administration+and+smoking.">Cue dependency of nicotine self-administration and smoking.</a> Pharmacol Biochem Behav. 70, 515-530 (2001).</li><li>Cain, M. E., Green, T. A., Bardo, M. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Environmental+enrichment+decreases+responding+for+visual+novelty.">Environmental enrichment decreases responding for visual novelty.</a> Behavioural Processes. 73, 360-366 (2006).</li><li>Thompson, T. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Visual+Reinforcement+in+Siamese+Fighting+Fish.">Visual Reinforcement in Siamese Fighting Fish.</a> Science. 141, 55-57 (1963).</li><li>Blatter, K., Schultz, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Rewarding+properties+of+visual+stimuli.">Rewarding properties of visual stimuli.</a> Exp Brain Res. 168, 541-546 (2006).</li><li>Olsen, C. M., Winder, D. 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I., Pieper, J. O., Hamilton, L. R., Wise, R. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Qualitative+differences+between+C57BL/6J+and+DBA/2J+mice+in+morphine+potentiation+of+brain+stimulation+reward+and+intravenous+self-administration.">Qualitative differences between C57BL/6J and DBA/2J mice in morphine potentiation of brain stimulation reward and intravenous self-administration.</a> Psychopharmacology (Berl). 208, 309-321 (2010).</li></ol>

Sensación operante que buscan es una alternativa útil a drogas por vía intravenosa la auto-administración cuando el ratón es el animal de elección. El hecho de que ni la cirugía ni el mantenimiento del catéter que se requiere es ventajosa, ya que éstas son importantes obstáculos técnicos en el ratón. OSS también es atractivo porque puede ser la medición de los aspectos de refuerzo diferencia de otros reforzadores naturales como los alimentos. Es útil señalar que las medidas d...

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		<th>Material Name</th>
		<th>Type</th>
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<td>Drug self-administration test package for mouse: extra-wide chamber and retractable levers</td>
<td>&nbsp;</td>
<td><a href="http://www.med-associates.com/">Med Associates, Inc</a></td>
<td>MED-307W-CT-D1</td>
<td>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.</td>
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<td>Interface and software package</td>
<td>&nbsp;</td>
<td><a href="http://www.med-associates.com/">Med Associates, Inc</a></td>
<td>MED-SYST-16</td>
<td>This is the package for up to 16 chambers.</td>
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operant sensation seeking in the mouse

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.

Watch this Scientific Journal Video about Operant Sensation Seeking in the Mouse at JoVE.com

Operant Sensation Seeking in the Mouse

En este protocolo se describe un método de aprendizaje operante con estímulos sensoriales como un refuerzo en el ratón. Que no requiere formación previa o la restricción de alimentos, y que permite el estudio de la conducta motivada, sin el uso de un reforzador farmacológico o naturales, tales como los alimentos.

Sensación operante Buscando en el ratón

Operant methods are powerful behavioral tools for the study of motivated behavior.  These 'self-administration' methods have been used extensively in drug ...

Research

JoVE Journal

Neuroscience

A Procedure for Studying the Footshock-Induced Reinstatement of Cocaine Seeking in Laboratory Rats

Un procedimiento para el estudio de la reposición de estímulo eléctrico plantar inducido por la cocaína Buscando en ratas de laboratorio

The most insidious aspect of drug addiction is the high propensity for relapse.  Animal models of relapse, known as reinstatement procedures, have been ...

Investigación

Neurociencias

Multiple-mouse Neuroanatomical Magnetic Resonance Imaging

Múltiples imágenes del ratón neuroanatómicos de Resonancia Magnética

The field of mouse phenotyping with magnetic resonance imaging (MRI) is rapidly growing, motivated by the need for improved tools for characterizing and ...

Detection of Neuritic Plaques in Alzheimer's Disease Mouse Model

La detección de placas neuríticas en el modelo de la enfermedad de Alzheimer ratón

Alzheimer's disease (AD) is the most common neurodegenerative disorder leading to dementia. Neuritic plaque formation is one of the pathological hallmarks ...

The Mouse Forced Swim Test

El ratón de prueba de natación forzada

The forced swim test is a rodent behavioral test used for evaluation of antidepressant drugs, antidepressant efficacy of new compounds, and experimental ...

Microdialysis of Ethanol During Operant Ethanol Self-administration and Ethanol Determination by Gas Chromatography

Microdiálisis de etanol durante etanol operante determinación y la auto-administración de etanol por cromatografía de gases

Operant self-administration methods are commonly used to study the behavioral and pharmacological effects of many drugs of abuse, including ethanol.  ...

Intracerebroventricular Viral Injection of the Neonatal Mouse Brain for Persistent and Widespread Neuronal Transduction

Inyección Viral Intracerebroventricular de Neonatología del ratón Cerebro de transducción neuronal persistente y generalizada

With the pace of scientific advancement accelerating rapidly, new methods are needed for experimental neuroscience to quickly and easily manipulate gene ...

A Simple Way to Measure Alterations in Reward-seeking Behavior Using Drosophila melanogaster

A Simple Way to Measure Alterations in Reward-seeking Behavior Using Drosophila melanogaster

Una manera sencilla de medir alteraciones en el comportamiento de búsqueda de recompensa Uso<em&gt; Drosophila melanogaster</em

We describe a protocol for measuring ethanol self-administration in fruit flies (Drosophila melanogaster) as a proxy for changes in reward states. We ...

Operant Protocols for Assessing the Cost-benefit Analysis During Reinforced Decision Making by Rodents

Operante protocolos para evaluar el análisis de costo-beneficio en decisiones reforzadas por roedores

Reinforcement-guided decision making is the ability to choose between competing courses of action based on the relative value of the benefits and their ...

Transpupillary Two-Photon In Vivo Imaging of the Mouse Retina

Imágenes transpupilares de dos fotones in vivo de la retina del ratón

The retina transforms light signals from the environment into electrical signals that are propagated to the brain. Diseases of the retina are prevalent ...

In vivo Calcium Imaging in Mouse Inferior Olive

In vivo Calcium Imaging in Mouse Inferior Olive

In vivo Imágenes de calcio en la aceituna inferior de ratón

Inferior olive (IO), a nucleus in the ventral medulla, is the only source of climbing fibers that form one of the two input pathways entering the ...