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

פרויקט זה נתמך על ידי NIH מענקים DA19112 (DGW) ו DA026994 (CMO). איור סופק על ידי קתרין Louderback. ניסויים שבוצעו במעבדה ונדרבילט Murine neurobehavioral.

1. כתוב תוכנית לרוץ הפעלות מבחן אופרנטית באמצעות גירויים חזותיים וקוליים מגוונים כמו חיזוק <ol style=";text-align:right;direction:rtl"><li style=";text-align:right;direction:rtl"> עבור (FR) מפגשים קבועים יחס: להפוך את המפגשים שעה אחת באורך באור הבית מאוורר מופעל במהלך הפגישה. הפעלות יחס פרוגרסיבי, לעשות מפג...

<ol>
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J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Development+of+pharmacotherapies+for+drug+addiction:+a+Rosetta+stone+approach.">Development of pharmacotherapies for drug addiction: a Rosetta stone approach.</a> Nat Rev Drug Discov. 8, 500-515 (2009).</li><li>Arnold, J. M., Roberts, D. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+critique+of+fixed+and+progressive+ratio+schedules+used+to+examine+the+neural+substrates+of+drug+reinforcement.">A critique of fixed and progressive ratio schedules used to examine the neural substrates of drug reinforcement.</a> Pharmacol Biochem Behav. 57, 441-447 (1997).</li><li>O'Brien, C. P., Gardner, E. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Critical+assessment+of+how+to+study+addiction+and+its+treatment:+human+and+non-human+animal+models.">Critical assessment of how to study addiction and its treatment: human and non-human animal models.</a> Pharmacology &#38; Therapeutics. 108, 18-58 (2005).</li><li>Olsen, C. M., Duvauchelle, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prefrontal+cortex+D1+modulation+of+the+reinforcing+properties+of+cocaine.">Prefrontal cortex D1 modulation of the reinforcing properties of cocaine.</a> Brain Research. 1075, 229-235 (2006).</li><li>Epstein, D. H., Preston, K. L., Stewart, J., Shaham, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Toward+a+model+of+drug+relapse:+an+assessment+of+the+validity+of+the+reinstatement+procedure.">Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure.</a> Psychopharmacology (Berl). 189, 1-16 (2006).</li><li>Kalivas, P. W., McFarland, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Brain+circuitry+and+the+reinstatement+of+cocaine-seeking+behavior.">Brain circuitry and the reinstatement of cocaine-seeking behavior.</a> Psychopharmacology (Berl). 168, 44-56 (2003).</li><li>Stewart, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pathways+to+relapse:+the+neurobiology+of+drug-+and+stress-induced+relapse+to+drug-taking.">Pathways to relapse: the neurobiology of drug- and stress-induced relapse to drug-taking.</a> J Psychiatry Neurosci. 25, 125-136 (2000).</li><li>Olsen, C. M., Winder, D. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+method+for+single-session+cocaine+self-administration+in+the+mouse.">A method for single-session cocaine self-administration in the mouse.</a> Psychopharmacology (Berl). 187, 13-21 (2006).</li><li>Rocha, B. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Differential+responsiveness+to+cocaine+in+C57BL/6J+and+DBA/2J+mice.">Differential responsiveness to cocaine in C57BL/6J and DBA/2J mice.</a> Psychopharmacology (Berl). 138, 82-88 (1998).</li><li>Caine, S. B., Negus, S. S., Mello, N. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Method+for+training+operant+responding+and+evaluating+cocaine+self-administration+behavior+in+mutant+mice.">Method for training operant responding and evaluating cocaine self-administration behavior in mutant mice.</a> Psychopharmacology (Berl). 147, 22-24 (1999).</li><li>Colby, C. R., Whisler, K., Steffen, C., Nestler, E. J., Self, D. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Striatal+cell+type-specific+overexpression+of+DeltaFosB+enhances+incentive+for+cocaine.">Striatal cell type-specific overexpression of DeltaFosB enhances incentive for cocaine.</a> J Neurosci. 23, 2488-2493 (2003).</li><li>Schramm-Sapyta, N. L., Olsen, C. M., Winder, D. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cocaine+self-administration+reduces+excitatory+responses+in+the+mouse+nucleus+accumbens+shell.">Cocaine self-administration reduces excitatory responses in the mouse nucleus accumbens shell.</a> Neuropsychopharmacology. 31, 1444-1451 (2006).</li><li>Steiner, R. C., Hsiung, H. M., Picciotto, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cocaine+self-administration+and+locomotor+sensitization+are+not+altered+in+CART+knockout+mice.">Cocaine self-administration and locomotor sensitization are not altered in CART knockout mice.</a> Behav Brain Res. 171, 56-62 (2006).</li><li>Marx, M. H., Henderson, R. L., Roberts, C. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Positive+reinforcement+of+the+bar-pressing+response+by+a+light+stimulus+following+dark+operant+pretests+with+no+after+effect.">Positive reinforcement of the bar-pressing response by a light stimulus following dark operant pretests with no after effect.</a> J Comp Physiol Psychol. 48, 73-76 (1955).</li><li>Baron, A., Kish, G. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Low-intensity+auditory+and+visual+stimuli+as+reinforcers+for+the+mouse.">Low-intensity auditory and visual stimuli as reinforcers for the mouse.</a> J Comp Physiol Psychol. 55, 1011-1013 (1962).</li><li>Stewart, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Reinforcing+effects+of+light+as+a+function+of+intensity+and+reinforcement+schedule.">Reinforcing effects of light as a function of intensity and reinforcement schedule.</a> Journal of comparative and physiological psychology. 53, 187-193 (1960).</li><li>Caggiula, A. 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. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Operant+sensation+seeking+engages+similar+neural+substrates+to+operant+drug+seeking+in+C57+mice.">Operant sensation seeking engages similar neural substrates to operant drug seeking in C57 mice.</a> Neuropsychopharmacology. 34, 1685-1694 (2009).</li><li>Crabbe, J. C., Wahlsten, D., Dudek, B. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Genetics+of+mouse+behavior:+interactions+with+laboratory+environment.">Genetics of mouse behavior: interactions with laboratory environment.</a> Science. 284, 1670-1672 (1999).</li><li>Crawley, J. N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Behavioral+phenotypes+of+inbred+mouse+strains:+implications+and+recommendations+for+molecular+studies.">Behavioral phenotypes of inbred mouse strains: implications and recommendations for molecular studies.</a> Psychopharmacology (Berl). 132, 107-124 (1997).</li><li>Belknap, J. K., Metten, P., Beckley, E. H., Crabbe, J. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Multivariate+analyses+reveal+common+and+drug-specific+genetic+influences+on+responses+to+four+drugs+of+abuse.">Multivariate analyses reveal common and drug-specific genetic influences on responses to four drugs of abuse.</a> Trends Pharmacol Sci. 29, 537-543 (2008).</li><li>Mozhui, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Strain+differences+in+stress+responsivity+are+associated+with+divergent+amygdala+gene+expression+and+glutamate-mediated+neuronal+excitability.">Strain differences in stress responsivity are associated with divergent amygdala gene expression and glutamate-mediated neuronal excitability.</a> J Neurosci. 30, 5357-5367 (2010).</li><li>Hefner, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impaired+fear+extinction+learning+and+cortico-amygdala+circuit+abnormalities+in+a+common+genetic+mouse+strain.">Impaired fear extinction learning and cortico-amygdala circuit abnormalities in a common genetic mouse strain.</a> J Neurosci. 28, 8074-8085 (2008).</li><li>Elmer, G. 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>

תחושה אופרנטית המבקשים היא אלטרנטיבה יעילה סמים תוך ורידית מינהל עצמי כאשר העכבר הוא בעל החיים של בחירה. העובדה כי לא ניתוח ולא תחזוקה קטטר שנדרש הוא יתרון, שכן הם מהווים מכשולים טכניים משמעותיים העכבר. OSS הוא גם מושך כי הוא עשוי להיות מדידת ההיבטים של חיזוק נבדל החיז?...

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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

בפרוטוקול זה אנו מתארים שיטה של ​​למידה אופרנטית באמצעות גירויים חושיים כמו חיזוק בתוך העכבר. זה לא דורש הכשרה מוקדמת או הגבלת מזון, והיא מאפשרת לימוד של התנהגות מוטיבציה ללא שימוש חיזוק תרופתי או טבעי כמו מזון.

Sensation Seeking אופרנטית ב העכבר

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

Research

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Neuroscience

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

נוהל לימוד החזרה Footshock-induced של קוקאין מחפשים אצל חולדות מעבדה

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

Multiple-mouse Neuroanatomical Magnetic Resonance Imaging

מרובה עכבר Neuroanatomical תהודה מגנטית

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

איתור של הפלאק מדלקת עצבים במודל מחלת אלצהיימר עכבר

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

עכבר בכפייה לשחות מבחן

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

Microdialysis של אתנול במהלך אתנול נחישות ממשל עצמי ואתנול אופרנטית על ידי גז כרומטוגרפיה

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

הזרקת נגיפי Intracerebroventricular של ילודים עכבר המוח לתמרה עצבית מתמשכת ונרחבת

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

דרך פשוטה למדוד שינויים בהתנהגות שוחרת זכה שימוש<em&gt; תסיסנית</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

פרוטוקולים operant להערכת ניתוח עלות-תועלת במהלך קבלת החלטות מחוזק על ידי מכרסמים

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

הדמיה טרנס-אימונית של שני פוטונים In vivo של רשתית העכבר

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

אין ויוו הדמיית סידן בעכבר זית נחות

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 ...