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	<li>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=The+reinstatement+model+of+drug+relapse:+history,+methodology+and+major+findings.">The reinstatement model of drug relapse: history, methodology and major findings.</a> Psychopharmacology. 168 (1-2), 3-20 (2003).</li><li>de Wit, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Priming+effects+with+drugs+and+other+reinforcers.">Priming effects with drugs and other reinforcers.</a> Experimental and Clinical Psychopharmacology. 4, 5-10 (1996).</li><li>Bossert, J. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neurobiology+of+relapse+to+heroin+and+cocaine+seeking:+An+update+and+clinical+implications.">Neurobiology of relapse to heroin and cocaine seeking: An update and clinical implications.</a> Eur J Pharmacol. 526 (1-3), 36-50 (2005).</li><li>Shalev, U., Grimm, J. W., 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=Neurobiology+of+relapse+to+heroin+and+cocaine+seeking:+a+review.">Neurobiology of relapse to heroin and cocaine seeking: a review.</a> Pharmacol Rev. 54 (1), 1-42 (2002).</li><li>Shaham, Y., 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=Stress+reinstates+heroin-seeking+in+drug-free+animals:+an+effect+mimicking+heroin,+not+withdrawal.">Stress reinstates heroin-seeking in drug-free animals: an effect mimicking heroin, not withdrawal.</a> Psychopharmacology. 119, 334-341 (1995).</li><li>Shaham, Y., Erb, S., 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=Stress-induced+relapse+to+heroin+and+cocaine+seeking+in+rats:+a+review.">Stress-induced relapse to heroin and cocaine seeking in rats: a review.</a> Brain Res Brain Res Rev. 33 (1), 13-33 (2000).</li><li>Erb, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Central+injections+of+CRF+reinstate+cocaine+seeking+in+rats+after+postinjection+delays+of+up+to+3+h:+an+influence+of+time+and+environmental+context.">Central injections of CRF reinstate cocaine seeking in rats after postinjection delays of up to 3 h: an influence of time and environmental context.</a> Psychopharmacology (Berl). 187 (1), 112-120 (2006).</li><li>Erb, S., Shaham, Y., 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=Stress+reinstates+cocaine-seeking+behavior+after+prolonged+extinction+and+a+drug-free+period.">Stress reinstates cocaine-seeking behavior after prolonged extinction and a drug-free period.</a> Psychopharmacology. 128, 408-412 (1996).</li><li>Tran-Nguyen, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Time-dependent+changes+in+cocaine-seeking+behavior+and+extracellular+dopamine+levels+in+the+amygdala+during+cocaine+withdrawal.">Time-dependent changes in cocaine-seeking behavior and extracellular dopamine levels in the amygdala during cocaine withdrawal.</a> Neuropsychopharmacology. 19, 48-59 (1998).</li><li>Stretch, R., Gerber, G. J., Wood, S. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Factors+affecting+behavior+maintained+by+response-contingent+intravenous+infusions+of+amphetamine+in+squirrel+monkeys.">Factors affecting behavior maintained by response-contingent intravenous infusions of amphetamine in squirrel monkeys.</a> Canadian Journal of Physiology and Pharmacology. 49, 581-589 (1971).</li><li>Shaham, Y., Rodaros, D., 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=Reinstatement+of+heroin-reinforced+behavior+following+long-term+extinction+Implications+for+the+treatment+of+relapse+to+drug-taking.">Reinstatement of heroin-reinforced behavior following long-term extinction Implications for the treatment of relapse to drug-taking.</a> Behavioural Pharmacology. 5, 360-364 (1994).</li><li>Wit, H. d. e., 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=Reinstatement+of+cocaine-reinforced+responding+in+the+rat.">Reinstatement of cocaine-reinforced responding in the rat.</a> Psychopharmacology. 75, 134-143 (1981).</li><li>Erb, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Alpha-2+adrenergic+receptor+agonists+block+stress-induced+reinstatement+of+cocaine+seeking.">Alpha-2 adrenergic receptor agonists block stress-induced reinstatement of cocaine seeking.</a> Neuropsychopharmacology. 23 (2), 138-150 (2000).</li><li>Shalev, U. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stress+and+relapse+to+drug+seeking+in+rats:+studies+on+the+generality+of+the+effect.">Stress and relapse to drug seeking in rats: studies on the generality of the effect.</a> Psychopharmacology (Berl). 150, 337-346 (2000).</li></ol>

وقد أجريت تجارب على الحيوانات وفقا للمبادئ التوجيهية واللوائح التي وضعها المجلس الكندي لرعاية الحيوان وجامعة تورنتو جنة رعاية الحيوان. وقد رعت إنتاج هذا الفيديو من قبل شركة ميد ، الزميلة التي تنتج الأداة المستخدمة في هذه المقالة.

على مدى العقود القليلة الماضية ، تم وضع ثلاثة بدائل لإعادة SA الداخلي لدراسة إعادة المخدرات تسعى لذلك في الفئران المختبرية والقردة. الخلافات التي تحدد الاختلافات الإجرائية تتعلق في المقام الأول إلى المخدرات سواء SA ، الانقراض ، وتحدث خلال جلسات الاختبار في نفس اليوم أو في أيام مختلفة 1. ويشار إلى الإجراء التي وصفناها في هذه الورقة على أنها (أي ، بطريقة بين الدورة) &quot;في غضون بين&quot; التغيير الدورة ، لأن المخدرات SA يحدث أثناء الجلسات اليومية التي تكون منفصلة من الانقراض ودورات الاختبار ، ولكن خطر الانقراض والاختبار تحدث في نفس اليوم (أي بطريقة ضمن الدورة) [على سبيل المثال ، 7 ، 9]. بدلا من ذلك ، في ما يسمى &quot;بين الدورتين&quot; الإجراءات وجميع مراحل التجربة تحدث بالتسلسل ، بحيث تعطى SA ، الانقراض ، وجلسات الاختبار في أيام مختلفة (أي جميع المراحل ما بين الدورات) [على سبيل المثال ، 8 ، 10 ، 11]. في المقابل ، في إجراءات كاملة &quot;ضمن جلسات&quot; ، SA التدريب ، والانقراض ، وتحدث عن جلسات اختبار في نفس اليوم [على سبيل المثال ، 12]. وإن كانت هناك تقارير نشرت footshock بفعل إعادة المخدرات باستخدام أشكال مختلفة تسعى لإعادة إجراء ، وجدنا هذه الضغوطات (على الأقل في الحيوانات ذات تاريخ طويل من الكوكايين SA) لتكون أكثر فعالية عندما يحدث الانقراض والاختبار على نفسه اليوم (أي في &quot;في غضون بين&quot; بطريقة دورات). بدلا من ذلك ، لقد حققنا نجاحا في الحصول على موثوقية footshock بفعل إعادة استخدام الكوكايين تسعى تماما &quot;بين الدورتين&quot; الداخلي ، ولكن فقط في ظل الظروف التي يتم فيها إيواء الحيوانات في غرف SA في كافة مراحل التجربة 8 ، أو على الأقل خلال الانقراض والاختبار 13. والعيب في هذا النهج بين الدورة ، على مدى تلك الموصوفة في هذا البروتوكول ، هو أنه يحد من عدد من الموضوعات التي يمكن تدريبها واختبارها في وقت واحد ، وبالتالي يقلل من كفاءة جمع البيانات. على الرغم من تحت شروط هذا البروتوكول يمكن أن تسقط واحدة فقط مجموعة من الحيوانات واختبارها في وقت معين ، يمكن أن يتحقق قدر أكبر من سرعة مذهلة من قبل أسبوع واحد وقت بدء مرحلة التدريب SA لمجموعتين من الفئران. في هذا السيناريو ، يمكن أن المجموعة الأولى من الفئران الدخول في مرحلة خالية من المخدرات في المجموعة الثانية يدخل أسبوع 2 من التدريب SA ، وبالتالي ، يمكن أن يتم من الانقراض والاختبار في المجموعة الأولى في حين أن المجموعة الثانية والخمسين في المخدرات خالية من المرحلة. هذا النهج يتيح استخداما أكثر كفاءة للموارد وتسارع معدل الحصول على البيانات ، في حين تؤدي إلى إعادة footshock التي يسببها فعالة جدا وموثوق بها. الأهم من ذلك ، في إجراء لدينا ، انقراض السلوك سابقا المخدرات المقوى واختبار لإعادة يحدث في وجود المخدرات المرتبطة العظة. على الرغم من أننا لم تنفذ التدريب الانقراض أو الاختبار في حال عدم وجود منبهات المرتبطة بالمخدرات ، فمن فهمنا ، استنادا إلى الاتصالات الشخصية ، وبأن الضغوطات قد تكون في الواقع غير فعالة في إحداث إعادة الاختبار عندما تحدث في غياب انطفأت اشارات ( على الأقل في حالة الحيوانات ذات تاريخ طويل من الكوكايين SA). الفحص المنتظم لهذا المتغير ، والآثار المترتبة عليه يشكل النظرية ، هو مسألة هامة للبحث في المستقبل. وثمة عامل أخير الاجرائية التي تضمن التعليق هو أن تأثير التوتر على إعادة footshock يبدو أن حساسية عالية تجاه التلاعب من السياق. على سبيل المثال ، والإجهاد footshock هو الوحيد الفعال في إحداث بإعادة المخدرات تسعى إذا تم تناوله في البيئة التي SA المخدرات وتحدث الانقراض ، وهذا هو ، لا إعادة footshock المخدرات تسعى إذا التعرض للإجهاد يحدث في سياق الرواية ، مما يدل على أهمية التفاعل بين الضغوطات والبيئة المخدرات في آثاره على إعادة 14. في إبرامها وإجراءات إعادة footshock ، مثل تلك التي وصفها في هذه الورقة ، التي استخدمت بنجاح كبير لتوضيح الآليات الأساسية السلوكية والعصبية الحيوية التي تحكم العلاقة بين الاجهاد والانتكاس المخدرات. في الواقع ، فإن هذه الإجراءات ، وعند تعديلها لاستيعاب المعالجة المسبقة الدوائية أو الكيميائية العصبية التي تستهدف التلاعب العصبية ركائز محددة ، يمكن أن تكون بمثابة أدوات قوية للتميز في بيولوجيا الأعصاب إلى إعادة المخدرات التي تسعى الإجهاد.

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<td>Basic Drug Self-Administration Test Package for Rat Package Component</td>
<td><a href="http://www.med-associates.com/">Med Associates, Inc</a></td>
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<td><a href="http://www.med-associates.com/">Med Associates, Inc</a></td>
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<td>Patented quick disconnect harness for stainless steel grid floor</td>
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<td><a href="http://www.med-associates.com/">Med Associates, Inc</a></td>
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<td><a href="http://www.med-associates.com/">Med Associates, Inc</a></td>
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a procedure for studying the footshock-induced reinstatement of cocaine seeking in laboratory rats

الجانب الأكثر غدرا من الإدمان على المخدرات هو النزوع عالية للانتكاس. وقد استخدمت النماذج الحيوانية من الانتكاس ، والمعروفة باسم إجراءات إعادة ، على نطاق واسع لدراسة بيولوجيا الأعصاب وعلم الظواهر الانتكاس إلى تعاطي المخدرات. على الرغم من الاختلافات الإجرائية ظهرت خلال العقود العديدة الماضية ، وتستند إجراءات إعادة الأكثر تقليدية على غرار المخدرات (SA) من الإدارة الذاتية. في هذا النموذج ، يتم تدريب حيوان لإجراء استثابي استجابة للحصول على المخدرات. بعد ذلك ، يتم إطفاء السلوك بواسطة تعزيز استجابة للوحدات تحتجزها. يتم تشغيل ثم إعادة تسعى المخدرات حدثا منفصلا بذاته ، مثل حقن المخدرات من التدريب ، والتعرض من جديد إلى المخدرات المرتبطة العظة ، أو التعرض لإجهاد 1. وقد وضعت أصلا لدراسة إجراءات إعادة قدرة التعرض الحاد غير المملوكة للدواء التدريب تسعى إلى إعادة المخدرات في الفئران والقرود 1 و 2. ومنذ ذلك الحين تم تعديل إجراءات إعادة دراسة دور المحفزات البيئية ، بما في ذلك المخدرات المرتبطة العظة والتعرض لأشكال مختلفة من الإجهاد ، في الانتكاس إلى المخدرات التي تسعى 1 ، 3 ، 4. على مدى السنوات ال 15 الماضية ، كان التركيز الرئيسي للأدب على إعادة دور الإجهاد في الانتكاس المخدرات. واحدة من الأشكال الأكثر شيوعا من الاجهاد لدراسة هذه العلاقة هو التعرض الحاد لطيفة ، footshocks ، متقطعة الكهربائية. وقد تجلى في الأصل من قدرة الضغط footshock للحث على إعادة المخدرات التي تسعى شاهام وزملاؤه (1995) في الفئران التي لها تاريخ في SA الهيروين عن طريق الوريد 5. لاحقا ، كان التأثير المعمم للفئران ذات التاريخ من الكوكايين في الوريد ، الميثامفيتامين والنيكوتين SA ، وكذلك عن طريق الفم الايثانول SA 3 و 6. على الرغم من أن يمكن تحقيقه footshock بفعل إعادة تسعى المخدرات وموثوق بها بقوة ، فهو التأثير الذي يميل إلى أن يكون حساسة إلى متغيرات parametrical معينة. وتشمل هذه الترتيبات من جلسات اختبار الانقراض وإعادة وحدتها ومدتها من الإجهاد footshock ، ووجود المخدرات المرتبطة الانقراض خلال العظة والاختبار من أجل اعادته. هنا نقدم بروتوكول للfootshock بفعل إعادة تسعى من الكوكايين التي استخدمناها مع نجاح مستمرة لدراسة العلاقة بين التوتر والسعي الكوكايين.

Watch this Scientific Journal Video about A Procedure for Studying the Footshock-Induced Reinstatement of Cocaine Seeking in Laboratory Rats at JoVE.com

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

وقد استخدمت النماذج الحيوانية من الانتكاس ، والمعروفة باسم إجراءات إعادة ، على نطاق واسع لدراسة دور الإجهاد في الانتكاس إلى السعي المخدرات. هنا ، ونحن تقريرا عن طريقة لحفز إعادة تسعى من الكوكايين في فئران التجارب عن طريق التعرض الحاد المتقطع footshock معتدل ، الكهربائية.

إجراء دراسة لإعادة Footshock الناتج عن السعي من الكوكايين في فئران التجارب

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

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20.7K Views.  University of Toronto Scarborough. وقد استخدمت النماذج الحيوانية من الانتكاس ، والمعروفة باسم إجراءات إعادة ، على نطاق واسع لدراسة دور الإجهاد في الانتكاس إلى السعي المخدرات. هنا ، ونحن تقريرا عن طريقة لحفز إعادة تسعى من الكوكايين في فئران التجارب عن طريق التعرض الحاد المتقطع footshock معتدل ، الكهر?...

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

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.

In this protocol we describe a method of operant learning using sensory stimuli as a reinforcer in the mouse. It requires no prior training or food restriction, and it allows the study of motivated behavior without the use of a pharmacological or natural reinforcer such as food.

استثابي الإحساس المفضل في الماوس

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

Muscle Receptor Organs in the Crayfish Abdomen: A Student Laboratory Exercise in Proprioception

The primary purpose of this experiment is to demonstrate primary sensory neurons conveying information of joint movements and positions as proprioceptive information for an animal. An additional objective of this experiment is to learn anatomy of the preparation by staining, dissection and viewing of neurons and sensory structures under a dissecting microscope. This is performed by using basic neurophysiological equipment to record the electrical activity from a joint receptor organ and staining techniques. The muscle receptor organ (MRO) system in the crayfish is analogous to the intrafusal muscle spindle in mammals, which aids in serving as a comparative model that is more readily accessible for electrophysiological recordings. In addition, these are identifiable sensory neurons among preparations. The preparation is viable in a minimal saline for hours which is amenable for student laboratory exercises. The MRO is also susceptible to neuromodulation which encourages intriguing questions in the sites of modulatory action and integration of dynamic signals of movements and static position along with a gain that can be changed in the system.

The primary purpose of this experiment is to understand how primary sensory neurons convey information of joint movements and positions as proprioceptive information for an animal. An additional objective of this report is present the anatomy of the preparation by dissection and viewing of neurons under a dissecting microscope.

هيئات مستقبلات العضلات في البطن جراد البحر : تمرين الطلاب في مختبر استقبال الحس العميق

The primary purpose of this experiment is to demonstrate primary sensory neurons conveying information of joint movements and positions as proprioceptive ...

A General Method for Evaluating Incubation of Sucrose Craving in Rats

For someone on a food-restricted diet, food craving in response to food-paired cues may serve as a key behavioral transition point between abstinence and relapse to food taking 1. Food craving conceptualized in this way is akin to drug craving in response to drug-paired cues. A rich literature has been developed around understanding the behavioral and neurobiological determinants of drug craving; we and others have been focusing recently on translating techniques from basic addiction research to better understand addiction-like behaviors related to food 2-4.
As done in previous studies of drug craving, we examine sucrose craving behavior by utilizing a rat model of relapse. In this model, rats self-administer either drug or food in sessions over several days. In a session, lever responding delivers the reward along with a tone+light stimulus. Craving behavior is then operationally defined as responding in a subsequent session where the reward is not available. Rats will reliably respond for the tone+light stimulus, likely due to its acquired conditioned reinforcing properties 5. This behavior is sometimes referred to as sucrose seeking or cue reactivity. In the present discussion we will use the term "sucrose craving" to subsume both of these constructs.
In the past decade, we have focused on how the length of time following reward self-administration influences reward craving. Interestingly, rats increase responding for the reward-paired cue over the course of several weeks of a period of forced-abstinence. This "incubation of craving" is observed in rats that have self-administered either food or drugs of abuse 4,6. This time-dependent increase in craving we have identified in the animal model may have great potential relevance to human drug and food addiction behaviors.
Here we present a protocol for assessing incubation of sucrose craving in rats. Variants of the procedure will be indicated where craving is assessed as responding for a discrete sucrose-paired cue following extinction of lever pressing within the sucrose self-administration context (Extinction without cues) or as responding for sucrose-paired cues in a general extinction context (Extinction with cues).

Responding for food or drug-paired cues increases over the course of a period of abstinence and this may relate to an increased susceptibility to relapse behaviors. Here we detail a procedure for evaluating this "incubation of craving" in rats that have self-administered sucrose.

طريقة عامة لتقييم الحضانة لالتوق السكروز في الجرذان

For someone on a food-restricted diet, food craving in response to food-paired cues may serve as a key behavioral transition point between abstinence and ...

Rapid Determination of the Thermal Nociceptive Threshold in Diabetic Rats

Painful diabetic neuropathy (PDN) is characterized by hyperalgesia i.e., increased sensitivity to noxious stimulus, and allodynia i.e., hypersensitivity to normally innocuous stimuli1. Hyperalgesia and allodynia have been studied in many different rodent models of diabetes mellitus2. However, as stated by B&ouml;lcskei et al, determination of "pain" in animal models is challenging due to its subjective nature3. Moreover, the traditional methods used to determine behavioral responses to noxious thermal stimuli usually lack reproducibility and pharmacological sensitivity3. For instance, by using the hot-plate method of Ankier4, flinch, withdrawal and/or licking of either hind- and/or fore-paws is quantified as reflex latencies at constant high thermal stimuli (52-55 &deg;C). However, animals that are hyperalgesic to thermal stimulus do not reproducibly show differences in reflex latencies using those supra-threshold temperatures3,5. As the recently described method of B&ouml;lcskei et al.6, the procedures described here allows for the rapid, sensitive and reproducible determination of thermal nociceptive thresholds (TNTs) in mice and rats. The method uses slowly increasing thermal stimulus applied mostly to the skin of mouse/rat plantar surface. The method is particularly sensitive to study anti-nociception during hyperalgesic states such as PDN. The procedures described bellow are based on the ones published in detail by Alm&aacute;si et al 5 and B&ouml;lcskei et al 3. The procedures described here have been approved the Laboratory Animal Care and Use Committee (LACUC), Wright State University.

Here, we describe a rapid reliable and simple procedure to determine the lowest temperature at which rats or mice show nocifensive behavior, i.e. the thermal nociceptive threshold (TNT). This method applies a slowly increasing thermal stimulus allowing precise and reproducible estimation of TNTs with minimum, if any, stress to the animals.

سريع تحديد العتبة Nociceptive الحرارية في الفئران المصابة بمرض السكر

Painful diabetic neuropathy (PDN) is characterized by hyperalgesia i.e., increased sensitivity to noxious stimulus, and allodynia i.e., hypersensitivity ...

Methods for Studying the Mechanisms of Action of Antipsychotic Drugs in Caenorhabditis elegans

Caenorhabditis elegans is a simple genetic organism amenable to large-scale forward and reverse genetic screens and chemical genetic screens. The C. elegans genome includes potential antipsychotic drug (APD) targets conserved in humans, including genes encoding proteins required for neurotransmitter synthesis and for synaptic structure and function. APD exposure produces developmental delay and/or lethality in nematodes in a concentration-dependent manner. These phenotypes are caused, in part, by APD-induced inhibition of pharyngeal pumping1,2. Thus, the developmental phenotype has a neuromuscular basis, making it useful for pharmacogenetic studies of neuroleptics. Here we demonstrate detailed procedures for testing APD effects on nematode development and pharyngeal pumping. For the developmental assay, synchronized embryos are placed on nematode growth medium (NGM) plates containing APDs, and the stages of developing animals are then scored daily. For the pharyngeal pumping rate assay, staged young adult animals are tested on NGM plates containing APDs. The number of pharyngeal pumps per unit time is recorded, and the pumping rate is calculated. These assays can be used for studying many other types of small molecules or even large molecules.

Methods for Studying the Mechanisms of Action of Antipsychotic Drugs in Caenorhabditis elegans

Approaches for testing the effects of antipsychotic drugs (APDs) in Caenorhabditis elegans are demonstrated. Assays are described for testing drug effects on development and viability and on pharyngeal pumping rate. These methods are also applicable for pharmacogenetic experiments with drug classes other than APDs.

أساليب لدراسة آليات عمل المضادة للذهان من أدوية في<em&gt; انواع معينة ايليجانس</em

Caenorhabditis elegans is a simple genetic organism amenable to  large-scale forward and reverse genetic screens and chemical genetic screens. The C.  ...

An In Vitro Adult Mouse Muscle-nerve Preparation for Studying the Firing Properties of Muscle Afferents

Muscle sensory neurons innervating muscle spindles and Golgi tendon organs encode length and force changes essential to proprioception. Additional afferent fibers monitor other characteristics of the muscle environment, including metabolite buildup, temperature, and nociceptive stimuli. Overall, abnormal activation of sensory neurons can lead to movement disorders or chronic pain syndromes. We describe the isolation of the extensor digitorum longus (EDL) muscle and nerve for in vitro study of stretch-evoked afferent responses in the adult mouse. Sensory activity is recorded from the nerve with a suction electrode and individual afferents can be analyzed using spike sorting software. In vitro preparations allow for well controlled studies on sensory afferents without the potential confounds of anesthesia or altered muscle perfusion. Here we describe a protocol to identify and test the response of muscle spindle afferents to stretch. Importantly, this preparation also supports the study of other subtypes of muscle afferents, response properties following drug application and the incorporation of powerful genetic approaches and disease models in mice.

An In Vitro Adult Mouse Muscle-nerve Preparation for Studying the Firing Properties of Muscle Afferents

Muscle sensory neurons are involved in proprioceptor signaling and also report on metabolic state and injury related events. We describe an adult mouse in vitro muscle-nerve preparation for studies on stretch-activated muscle afferents.

و<em&gt; في المختبر</em&gt; ماوس الكبار إعداد العضلات العصبية لدراسة خصائص اطلاق Afferents العضلات

Muscle sensory neurons innervating muscle spindles and Golgi tendon organs encode length and force changes essential to proprioception. Additional ...

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

We describe a protocol for measuring ethanol self-administration in fruit flies (Drosophila melanogaster) as a proxy for changes in reward states. We demonstrate a simple way to tap into the fly reward system, modify experiences related to natural reward, and use voluntary ethanol consumption as a measure for changes in reward states. The approach serves as a relevant tool to study the neurons and genes that play a role in experience-mediated changes of internal state. The protocol is composed of two discrete parts: exposing the flies to rewarding and nonrewarding experiences, and assaying voluntary ethanol consumption as a measure of the motivation to obtain a drug reward. The two parts can be used independently to induce the modulation of experience as an initial step for further downstream assays or as an independent two-choice feeding assay, respectively. The protocol does not require a complicated setup and can therefore be applied in any laboratory with basic fly culture tools.

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

We describe a protocol for inducing rewarding and nonrewarding experiences in fruit flies (Drosophila melanogaster) using voluntary ethanol consumption as a measure for changes in reward states.

طريقة بسيطة لقياس التغيرات في السلوك المكافأة التماس طريق<em&gt; ذبابة الفاكهة</em

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

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

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.&#160;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.

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.

بروتوكول لقياس مفاعليه جديلة في نموذج الفئران من اضطراب استخدام الكوكايين

Cocaine use disorder (CUD) follows a trajectory of repetitive self-administration during which previously neutral stimuli gain incentive value. Cue ...

A Microbiomechanical System for Studying Varicosity Formation and Recovery in Central Neuron Axons

Axonal varicosities are enlarged structures along the shafts of axons with a high degree of heterogeneity. They are present not only in brains with neurodegenerative diseases or injuries, but also in the normal brain. Here, we describe a newly-established micromechanical system to rapidly, reliably, and reversibly induce axonal varicosities, allowing us to understand the mechanisms governing varicosity formation and heterogeneous protein composition. This system represents a novel means to evaluate the effects of compression and shear stress on different subcellular compartments of neurons, different from other in vitro systems that mainly focus on the effect of stretching. Importantly, owing to the unique features of our system, we recently made a novel discovery showing that the application of pressurized fluid can rapidly and reversibly induce axonal varicosities through the activation of a transient receptor potential channel. Our biomechanical system can be utilized conveniently in combination with drug perfusion, live cell imaging, calcium imaging, and patch clamp recording. Therefore, this method can be adopted for studying mechanosensitive ion channels, axonal transport regulation, axonal cytoskeleton dynamics, calcium signaling, and morphological changes related to traumatic brain injury.

This protocol describes a physiologically relevant, pressurized fluid approach for rapid and reversible induction of varicosities in neurons.

نظام ميكروبيوميتشانيكال لدراسة تشكيل فاريكوسيتي والانتعاش في محاور عصبية من الخلايا العصبية المركزية

Axonal varicosities are enlarged structures along the shafts of axons with a high degree of heterogeneity. They are present not only in brains with ...

Preparation of Peripheral Nerve Stimulation Electrodes for Chronic Implantation in Rats

Peripheral nerve cuff electrodes have long been used in the neurosciences and related fields for stimulation of, for example, vagus or sciatic nerves. Several recent studies have demonstrated the effectiveness of chronic VNS in enhancing central nervous system plasticity to improve motor rehabilitation, extinction learning, and sensory discrimination. Construction of chronically implantable devices for use in such studies is challenging due to rats&#8217; small size, and typical protocols require extensive training of personnel and time-consuming microfabrication methods. Alternatively, commercially available implantable cuff electrodes can be purchased at a significantly higher cost. In this protocol, we present a simple, low-cost method for construction of small, chronically implantable peripheral nerve cuff electrodes for use in rats. We validate the short and long-term reliability of our cuff electrodes by demonstrating that VNS in ketamine/xylazine anesthetized rats produces decreases in breathing rate consistent with activation of the Hering-Breuer reflex, both at the time of implantation and up to 10 weeks after device implantation. We further demonstrate the suitability of the cuff electrodes for use in chronic stimulation studies by pairing VNS with skilled lever press performance to induce motor cortical map plasticity.

Existing approaches for constructing chronically implantable peripheral nerve cuff electrodes for use in small rodents often require specialized equipment and/or highly trained personnel. In this protocol we demonstrate a simple, low-cost approach for fabricating chronically implantable cuff electrodes, and demonstrate their effectiveness for vagus nerve stimulation (VNS) in rats.

إعداد أقطاب تحفيز الأعصاب الطرفية للزرع المزمن في الفئران

Peripheral nerve cuff electrodes have long been used in the neurosciences and related fields for stimulation of, for example, vagus or sciatic nerves. ...