Die Autoren möchten die Finanzierung aus UL1TR000071 (NCATS), P30DK079638 (NIDDK), P30DA028821 (NIDA) und T32DA07287 (NIDA) bestätigen.

Alle Experimente sind in Übereinstimmung mit dem Leitfaden für die Pflege und Verwendung von Labortieren (Institut für Labortier Resources (US), 1996) und mit Zustimmung des Institutional Animal Care und Verwenden Ausschuss an der University of Texas Medical Branch. Ein. Themen <ol><li> Einfamilienhaus männlichen Sprague-Dawley-Ratten mit einem Gewicht von 225 bis 250 g bei 21 ° C und 30-50% relativer Luftfeuchte mit einem 12 Stunden Licht-Dunkel-Zyklus (Licht an 6.00-6: 12.00 Uhr). </li><li> Pflegen Ratten auf eine fettarme Ernährung (10% Fett von Energie). Gewöhnen Ratten, die Lebensmittel-und Kolonie Raum für mindestens 7 Tage vor dem Experiment. Die Tiere werden, um die Handhabung und Dosierung von Fahrzeug für drei Tage vor Beginn der Studien gewöhnt. Der erste Tag nach der Gewöhnung ist experimentell Tag 1. </li></ol> 2. Baseline Vorlieben <ol><li> Tag 1, füllen zwei saubere Lebensmittel Trichter, ein mit einem A und die andere mit B markiert, mit 10% Fett Essen für jeden Käfig. WEigh die Nahrungsmittelbehältern (mit Essen) und legen Sie sie in den Käfig, die Gewährleistung der Ratte hat Zugang zu beiden. </li><li> Tag 2, in etwa die gleiche Zeit, Essen Trichter wurden in den Käfig gelegt, bevor der Tag, notieren Sie die Futterraufe Gewichte und wechseln die Positionen der Trichter A und B. Dies mildert Trichter Position Bias. Immer prüfen die Heimkäfig für alle Lebensmittel aus dem Trichter entfernt, wiegen, und machen es. Die Nahrungsaufnahme wird durch Änderung der Trichter Gewicht zwischen Tagen gemessen. </li><li> Tag 3, notieren Sie die Futterraufe Gewichte wie zuvor. Untersuchen Sie die Menge der Nahrung in jeder Position und Futterraufe Futterraufe Identifikation (A und B) verbraucht. Diese Daten geben eine Grundlinie von der Lage und spezifischen Bias Trichter Vorlieben und sollte eine Vorliebe Punktzahl von ca. 50% haben, was keine Präferenz. Werfen Sie die restliche Essen. </li></ol> 3. Fat Vorlieben <ol><li> Tag 3, erhalten zwei saubere Lebensmittel Trichter für jeden Käfig. Es ist wichtig, saubere Lebensmittel Trichter verwendenwenn das Umschalten zwischen den verschiedenen Lebensmitteln zu verwirrende Düfte aus früheren Experimenten zu verhindern. Füllen Trichter A mit 12,5% Fett Essen und Trichter B mit 15% Fett Essen (Tabelle 1). Notieren Sie die Startgewichte jedes Trichters und legen sowohl in den Käfig. </li><li> Tag 4, notieren Sie die Gewichte der einzelnen Trichter, Schalt die Positionen der Trichter A und B auf Trichter legte sie zurück in den Käfig. </li><li> Tag 5, notieren Sie die Gewichte der einzelnen Behälter. Nach der Bestimmung der Gramm der einzelnen Lebensmittel an beiden Tagen verbraucht werden, können Lebensmittel Präferenz der Ratte bestimmt werden. </li><li> Die Schritte 3.1 bis 3.3 mehrfach mit den gleichen Tieren mit 12,5% Fett Nahrung im Vergleich zu Lebensmitteln mit zunehmendem Fettgehalt (z. B. die ersten 15%, neben 17,5%, dann 20% und schließlich 45% Fett). </li></ol> 4. Berechnungen und Datenanalyse <ol><li> Berechnung der täglichen Nahrungsaufnahme für jedes Tier durch Subtrahieren der endgültigen Masse des Nahrungs + Trichter von der Ausgangsmasse des Nahrungs+ Trichter. Da jedes Essen wird über 2 Tage gemessen wird, kann die 2 Tage insgesamt gemeinsam für jeden% Fett hinzugefügt werden. </li><li> Berechnen Sie die Fett Vorlieben Punktzahl durch Division der Einnahme des höheren Fett Lebensmittel aus der gesamten Lebensmittel über jeden Zeitraum von zwei Tagen verbraucht werden. Zum Beispiel, aß eine Ratte 8,9 g der 12,5% fettarme Ernährung und 27,5 g des 17,5%-Diät über 2 Tage. Daher die Vorliebe für diese Punktzahl einzelne Tier ist 76% (27,5 dividiert durch 36,4). </li><li> Mittelwert und die Graphen Präferenzwert für jede Diät (15%, 17,5%, 20% und 45% Fett) (Abbildung 3). Die gesamte Nahrungsaufnahme ist auch informative und kann leicht als Gramm (Fig. 4) aufgetragen werden. </li><li> Express den Vorzug Punktzahl (5A) und die Gesamtnahrungsaufnahme (5B) als Funktion der Gesamtenergieaufnahme (kcal) mit der Energiedichte in Tabelle 1. </li><li> Wenn mehr als eine Gruppe von Tieren, führen Sie eine Zwei-Wege-Wiederholunged misst ANOVA gefolgt von einem Bonferroni post-Test. Leistungsanalyse zeigt, daß n = 8 Tiere pro Gruppe zum Erfassen einer Differenz von 7% zwischen Behandlungsgruppen geeignet ist. </li></ol>

<ol>
	<li>Flegal, K. M., Carroll, M. D., Ogden, C. L., Curtin, L. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prevalence+and+trends+in+obesity+among+US+adults.">Prevalence and trends in obesity among US adults.</a> JAMA. 303 (3), 235-241 (1999).</li><li>Mokdad, A. H., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Prevalence+of+obesity,+diabetes,+and+obesity-related+health+risk+factors.">Prevalence of obesity, diabetes, and obesity-related health risk factors.</a> JAMA. 289 (1), 76-79 (2003).</li><li>Abete, I., Astrup, A., Mart&#237;nez, J. A., Thorsdottir, I., Zulet, M. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Obesity+and+the+metabolic+syndrome:+role+of+different+dietary+macronutrient+distribution+patterns+and+specific+nutritional+components+on+weight+loss+and+maintenance.">Obesity and the metabolic syndrome: role of different dietary macronutrient distribution patterns and specific nutritional components on weight loss and maintenance.</a> Nutr. Rev. 68 (4), 214-231 (2010).</li><li>Berthoud, H. R., M&#252;nzberg, H., Richards, B. K., Morrison, C. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neural+and+metabolic+regulation+of+macronutrient+intake+and+selection.">Neural and metabolic regulation of macronutrient intake and selection.</a> Proc. Nutr. Soc. 71 (3), 390-400 (2012).</li><li>Warwick, Z. S., Schiffman, S. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+dietary+fat+in+calorie+intake+and+weight+gain.">Role of dietary fat in calorie intake and weight gain.</a> Neurosci. Biobehav. Rev. 16 (4), 585-596 (1992).</li><li>Kendall, A., Levitsky, D. A., Strupp, B. J., Lissner, L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Weight+loss+on+a+low-fat+diet:+consequence+of+the+imprecision+of+the+control+of+food+intake+in+humans.">Weight loss on a low-fat diet: consequence of the imprecision of the control of food intake in humans.</a> Am. J. Clin. Nutr. 53 (5), 1124-1129 (1991).</li><li>Ackroff, K., Sclafani, A., Montmayeur, J. P., leCoutre, J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oral+and+Postoral+Determinants+of+Dietary+Fat+Appetite.">Oral and Postoral Determinants of Dietary Fat Appetite.</a> Fat Detection: Taste, Texture, and Post Ingestive Effects. Chapter 12. , (2010).</li><li>West, D. B., York, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dietary+fat,+genetic+predisposition,+and+obesity:+lessons+from+animal+models.">Dietary fat, genetic predisposition, and obesity: lessons from animal models.</a> Am. J. Clin. Nutr. 67, 505-512 (1998).</li><li>Sclafani, A., Ackroff, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Role+of+gut+nutrient+sensing+in+stimulating+appetite+and+conditioning+food+preferences.">Role of gut nutrient sensing in stimulating appetite and conditioning food preferences.</a> Am. J. Physiol. Regul. Integr. Comp. Physiol. 302 (10), (2012).</li><li>Velloso, L. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+brain+is+the+conductor:+diet-induced+inflammation+overlapping+physiological+control+of+body+mass+and+metabolism.">The brain is the conductor: diet-induced inflammation overlapping physiological control of body mass and metabolism.</a> Arq. Bras. Endocrinol. Metabol. 53 (2), 151-158 (2009).</li><li>Vanzela, E. C., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Pregnancy+restores+insulin+secretion+from+pancreatic+islets+in+cafeteria+diet-induced+obese+rats.">Pregnancy restores insulin secretion from pancreatic islets in cafeteria diet-induced obese rats.</a> Am. J. Physiol. Regul. Integr. Comp. Physiol. 298 (2), (2010).</li><li>Johnson, S. L., McPhee, L., Birch, L. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Conditioned+preferences:+young+children+prefer+flavors+associated+with+high+dietary+fat.">Conditioned preferences: young children prefer flavors associated with high dietary fat.</a> Physiol. Behav. 50 (6), 1245-1251 (1991).</li><li>Bolanos, C. A., Barrot, M., Berton, O., Wallace-Black, D., Nestler, E. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Methylphenidate+treatment+during+pre-+and+periadolescence+alters+behavioral+responses+to+emotional+stimuli+at+adulthood.">Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood.</a> Biol. Psychiatry. 54, 1317-1329 (2003).</li><li>Ignar, D. M., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Regulation+of+Ingestive+Behaviors+in+the+Rat+by+GSK1521498,+a+Novel+{micro}-Opioid+Receptor-Selective+Inverse+Agonist.">Regulation of Ingestive Behaviors in the Rat by GSK1521498, a Novel {micro}-Opioid Receptor-Selective Inverse Agonist.</a> J. Pharmacol. Exp. Ther. 339, 24-34 (2011).</li><li>Benzon, C. R., Johnson, S. B., McCue, D. L., Li, D., Green, T. A., Hommel, J. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Neuromedin+U+receptor+2+knockdown+in+the+paraventricular+nucleus+modifies+behavioral+responses+to+obesogenic+high-fat+food+and+leads+to+increased+body+weight.">Neuromedin U receptor 2 knockdown in the paraventricular nucleus modifies behavioral responses to obesogenic high-fat food and leads to increased body weight.</a> Neuroscience. , (2013).</li><li>Lucas, F., Ackroff, K., Sclafani, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dietary+fat-induced+hyperphagia+in+rats+as+a+function+of+fat+type+and+physical+form.">Dietary fat-induced hyperphagia in rats as a function of fat type and physical form.</a> Physiol Behav. 45 (5), 937-946 (1989).</li></ol>

Die Autoren haben nichts zu offenbaren.

The Fat Vorlieben Modell ist eine informative und leicht durchzuführen Assay von Fressverhalten. Dieser Test bietet die Möglichkeit, neuronale und molekularen Mechanismen, die die Nahrungsmittel Vorlieben, die ein wichtiger, aber wenig erforschten Bereich der Adipositas-Forschung zugrunde liegen, zu identifizieren. Veränderungen der Fett bevorzugt genetische Unterschiede oder pharmakologischen Manipulationen könnte so nach rechts oder links verschiebt in der Präferenz-Kurve (Fig. 3B) dargestellt we...

Adipositas ist eine weit verbreitete Problem in den Vereinigten Staaten ein, mit den Centers for Disease Control and Prevention schätzt, dass mehr als ein Drittel der amerikanischen Erwachsenen sind übergewichtig. Fettleibigkeit hat sich auch als Risikofaktor für zahlreiche gesundheitliche Bedenken, wie Typ-2-Diabetes, Bluthochdruck, hoher Cholesterinspiegel und 2 identifiziert. Während viele Faktoren haben gezeigt, dass die Zunahme der Fettleibigkeit zu beeinflussen, gibt es anhaltende Interesse und Kontroversen in der Rolle Makronährstoffe in 3,4 Fettleibigkeit spielen. Ein entscheidender Faktor für Übergewicht ist hoch Fettaufnahme 5. Erhöhte Nahrungsfett ist mit einem erhöhten Energieverbrauch Menschen 6 und signifikanter Anstieg der Körperfettgehalt 7,8 korreliert. Zusätzlich hat Nahrungsfett Belohnung Wert während und nach Verbrauch 7,9. Daher bestimmen, welche Faktoren Vorliebe für fettreiche Lebensmittel beeinflussen kann beide Führungs pharmakotherapeutische design und fördern das Verständnis der zugrunde liegenden Ernährung zu entscheiden, die zu Übergewicht führen kann. Das hier beschriebene Modell Fat Vorlieben testet für Ratten Präferenz zwischen Lebensmitteln mit unterschiedlichen Fettgehalt, aber ähnliche Nährwert. Insbesondere stellt dieses Modell der Ratten mit einer Auswahl von zwei verschiedenen Lebensmitteln gleichzeitig so dass die Quantifizierung der Präferenz auf der Basis des unteren Gramm Fett Essen Verse des höheren Fett Nahrung verbraucht. Pharmakologische und genetische Effekte können als eine Änderung der Präferenz für die Lebensmittel mit einem höheren Fettgehalt gemessen werden. The Fat Vorlieben Modell dient dazu, die weit verbreitet schmackhaft Nahrungsaufnahme 10 Modelle ergänzen, sondern bietet auch einige Vorteile. Dieses Modell ermöglicht es dem Experimentator speziell zur Bewertung Fressverhalten in einer kontrollierten Umgebung, in der zwei-Food-Optionen sind verfügbar. Traditionelle hohen Fettfutter Modelle bieten nur ein Lebensmittel, das die Fähigkeit zur Wahl der Lebensmittel studieren beseitigt, als eine wichtigeAspekt der menschlichen Nahrungsaufnahme. Einige Tests tun bieten mehrere Arten von Lebensmitteln und werden oft als &quot;Cafeteria&quot;-Typ Fütterungsstudien 11 bezeichnet. Diese Studien leiden an Reproduzierbarkeit, weil die menschliche Nahrung wird oft im Assay verwendet und ist nicht gut auf die Laborumgebung durch Nährstoff Variabilität geeignet. Wir verwenden definierte Diäten, die einzelnen Zutaten gereinigt somit stark verbessert Reproduzierbarkeit und Flexibilität, um Makronährstoffgehalt wie Nahrungsfett enthalten ändern. Bei höheren Fettaufnahme mit Adipositas beim Menschen 5 und der natürlichen menschlichen Vorliebe für fettreiche Lebensmittel höher 12, Behandlungen, die Ratte Vorliebe für fettreiche Lebensmittel können wertvolle Einblicke in die Fettleibigkeit bieten ändern verbunden.

<table border="0" cellpadding="0" cellspacing="0" width="673">
	<colgroup>
		<col />
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="22">
			<td height="22" style="height:22px;width:277px;">&#160;Rodent diet with 10 kcal% fat&#160;</td>
			<td style="width:111px;">Research Diets</td>
			<td style="width:119px;">D12450B</td>
			<td style="width:167px;">10 % fat rat food</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:277px;">&#160;Rodent diet with 12.5 kcal% fat&#160;</td>
			<td style="width:111px;">Research Diets</td>
			<td style="width:119px;">D07040501</td>
			<td>12.5 % fat rat food</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:277px;">&#160;Rodent diet with 15 kcal% fat&#160;</td>
			<td style="width:111px;">Research Diets</td>
			<td style="width:119px;">D07040502</td>
			<td>15 % fat rat food</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:277px;">&#160;Rodent diet with 17.5 kcal% fat&#160;</td>
			<td style="width:111px;">Research Diets</td>
			<td style="width:119px;">D07040503</td>
			<td>17.5 % fat rat food</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:277px;">&#160;Rodent diet with 20 kcal% fat&#160;</td>
			<td style="width:111px;">Research Diets</td>
			<td style="width:119px;">D07040504</td>
			<td>20 % fat rat food</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:277px;">&#160;Rodent diet with 45 kcal% fat&#160;</td>
			<td style="width:111px;">Research Diets</td>
			<td style="width:119px;">D12451</td>
			<td>45 % fat rat food</td>
		</tr>
		<tr height="22">
			<td height="22" style="height:22px;width:277px;">Rat feeders (3.75&#34;W x 2.875&#34;D x 5.25&#34;H)</td>
			<td style="width:111px;">Labex of MA</td>
			<td style="width:119px;">2528</td>
			<td>Food hoppers</td>
		</tr>
	</tbody>
</table>

fat preference: a novel model of eating behavior in rats

Adipositas ist ein wachsendes Problem in den Vereinigten Staaten von Amerika, mit mehr als einem Drittel der Bevölkerung als fettleibig eingestuft. Ein Faktor, der zu dieser multifaktoriellen Erkrankung ist der Verzehr einer fettreichen Diät, ein Verhalten, das gezeigt wurde, dass sowohl die Kalorienaufnahme und Körperfettgehalt zu erhöhen. Die Elemente der Regulierung Vorliebe für fettreiche Nahrung über andere Lebensmittel bleiben jedoch under. Um dieses Defizit zu überwinden, wurde ein Modell auf Veränderungen in der Präferenz für Nahrungsfett schnell und einfach testen, entwickelt. The Fat Vorlieben Modell präsentiert Ratten, die mit einer Reihe von Wahlmöglichkeiten zwischen Lebensmitteln mit unterschiedlichen Fettgehalt. Wie Menschen haben Ratten eine natürliche Tendenz zu aufwendig fettreiche Nahrung, so dass die Ratten-Modell ideal für translationale Studien. Änderungen der Präferenz der Wirkung entweder genetische oder pharmakologische Interventionen Unterschiede zurückzuführen. Dieses Modell ermöglicht die Erforschung der Determinanten von Fett Präferenz und Eindrehenkung pharmakotherapeutische Mitteln, die Einfluss auf Erwerb von Fettleibigkeit.

Ratten hatten physischen Zugang zu den beiden Lebensmittelbehältern gleichzeitig (Abbildung 1), um die Präferenz für die Auswahl von Lebensmitteln zur Verfügung mit unterschiedlichen Fettgehalt (Tabelle 1) zeigen. Ratte Essen wurde täglich gewogen und jede Nahrungsmittelspillage war schnell gefunden und machten (Abbildung 2). Verschütten von feinen Speisereste gefunden wurde minimal zu sein und nicht im Wesentlichen die Daten zu beeinflussen. Mit der Fat Vorlieben...

Watch this Scientific Journal Video about Fat Preference: A Novel Model of Eating Behavior in Rats at JoVE.com

Fat Preference: A Novel Model of Eating Behavior in Rats

Nahrungsfettgehalt beeinflusst sowohl Energieaufnahme und des Körperfettzusammensetzung bei Säugetieren. Durch die Untersuchung der Ratten Vorliebe für fettreiche Nahrung in einer Reihe von Experimenten Wahl, ist es möglich, die genetischen Unterschiede und pharmakologische Interventionen auf ihre Vorliebe für fettreiche Nahrung zu testen.

Fat Vorlieben: A Novel Modell des Essverhaltens bei Ratten

Obesity is a growing problem in the United States of America, with more than a third of the population classified as obese. One factor contributing to ...

fat-preference-a-novel-model-of-eating-behavior-in-rats

Research

JoVE Journal

Behavior

13.1K Aufrufe.  University of Texas Medical Branch.  Nahrungsfettgehalt beeinflusst sowohl Energieaufnahme und des Körperfettzusammensetzung bei Säugetieren. Durch die Untersuchung der Ratten Vorliebe für fettreiche Nahrung in einer Reihe von Experimenten Wahl, ist es möglich, die genetischen Unterschiede und pharmakologische Interventionen auf ihre Vorliebe für fettreiche Nahrung zu testen. 

Serie: Fat Preference: A Novel Model of Eating Behavior in Rats

Stereotaxic Microinjection of Viral Vectors Expressing Cre Recombinase to Study the Role of Target Genes in Cocaine Conditioned Place Preference

Microinjecting recombinant adenoassociated viral (rAAV) vectors expressing Cre recombinase into distinct mouse brain regions to selectively knockout genes of interest allows for enhanced temporally- and regionally-specific control of gene deletion, compared to existing methods. While conditional deletion can also be achieved by mating mice that express Cre recombinase under the control of specific gene promoters with mice carrying a floxed gene, stereotaxic microinjection allows for targeting of discrete brain areas at experimenter-determined time points of interest. In the context of cocaine conditioned place preference, and other cocaine behavioral paradigms such as self-administration or psychomotor sensitization that can involve withdrawal, extinction and/or reinstatement phases, this technique is particularly useful in exploring the unique contribution of target genes to these distinct phases of behavioral models of cocaine-induced plasticity. Specifically, this technique allows for selective ablation of target genes during discrete phases of a behavior to test their contribution to the behavior across time. Ultimately, this understanding allows for more targeted therapeutics that are best able to address the most potent risk factors that present themselves during each phase of addictive behavior.

This article describes how to microinject viral vectors into mouse brain and then test in a conditioned place preference paradigm that includes an acquisition, extinction and reinstatement phase.

Stereotaktische Mikroinjektion von viralen Vektoren ausdrücken Cre-Rekombinase, um die Rolle der Zielgene in Cocaine konditionierte Platzpräferenz Studieren

Microinjecting recombinant adenoassociated viral (rAAV) vectors expressing Cre recombinase into distinct mouse brain regions to selectively knockout genes ...

Forschung

Verhalten

A Procedure to Study the Effect of Prolonged Food Restriction on Heroin Seeking in Abstinent Rats

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during abstinence. Moreover, various environmental challenges can exacerbate this effect, as well as increase ongoing drug intake.
The procedure we describe here highlights the impact of a common environmental challenge, food restriction, on drug craving that is expressed as an augmentation of drug seeking in abstinent rats.
Rats are implanted with chronic intravenous i.v. catheters, and then trained to press a lever for i.v. heroin over a period of 10-12 days. Following the heroin self-administration phase the rats are removed from the operant conditioning chambers and housed in the animal care facility for a period of at least 14 days. While one group is maintained under unrestricted access to food (sated group), a second group (FDR group) is exposed to a mild food restriction regimen that results in their body weights maintained at 90% of their nonrestricted body weight. On day 14 of food restriction the rats are transferred back to the drug-training environment, and a drug-seeking test is run under extinction conditions (i.e.&#160;lever presses do not result in heroin delivery).
The procedure presented here results in a highly robust augmentation of heroin seeking on test day in the food restricted rats. In addition, compared to the acute food deprivation manipulations we have used before, the current procedure is a more clinically relevant model for the impact of caloric restriction on drug seeking. Moreover, it might be closer to the human condition as the rats are not required to go through an extinction-training phase before the drug-seeking test, which is an integral component of the popular reinstatement procedure.

A procedure that allows a demonstration of robust augmentation of drug seeking in food-restricted rats is described. Following heroin self-administration training, rats go through an abstinence period, in a drug-free environment, during which they are mildly food restricted. Drug seeking is then tested in the drug-associated environment.

Eine Vorgehensweise, um die Wirkung von Längerer Essen Beschränkung Heroin suche in abstinent Ratten untersucht

In human drug addicts, exposure to drug-associated cues or environments that were previously associated with drug taking can trigger relapse during ...

Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental disorder characterized by decreased reciprocal social interaction, abnormal communication, and repetitive behaviors with restricted interest. As diagnosis is based on clinical criteria, any potentially relevant rodent models of this heterogeneous disorder should ideally recapitulate these diverse behavioral traits. The BTBR T+ Itpr3tf/J (BTBR) mouse is an established animal model of ASD, displaying repetitive behaviors such as increased grooming, as well as cognitive inflexibility. With respect to social interaction and interest, the juvenile play test has been employed in multiple rodent models of ASD. Here, we show that when BTBR mice are tested in a juvenile social interaction enclosure containing sawdust bedding, they display a repetitive synchronous digging motion. This repetitive motor behavior, referred to as &#34;inchworming,&#34; was named because of the stereotypic nature of the movements exhibited by the mice while moving horizontally across the floor. Inchworming mice must use their fore- and hind-limbs in synchrony to displace the bedding, performing a minimum of one inward and one outward motion. Although both BTBR and C56BL/6J (B6) mice exhibit this behavior, BTBR mice demonstrate a significantly higher duration and frequency of inchworming and a decreased latency to initiate inchworming when placed in a bedded enclosure. We conclude that this newly described behavior provides a measure of a repetitive motor stereotypy that can be easily measured in animal models of ASD.

Inchworming: A Novel Motor Stereotypy in the BTBR T+ Itpr3tf/J Mouse Model of Autism

Inchworming is a highly repetitive synchronous digging motion displayed by BTBR T+ Itpr3tf/J (BTBR) mice when placed in a testing cage with sufficient sawdust bedding. The procedure is a modification of the juvenile social interaction protocol and is used here to assess repetitive motor stereotypies relevant to Autism Spectrum Disorder.

Inchworming: A Novel Motor Stereotypie in der BTBR<em&gt; T<sup&gt; +</sup&gt; Itpr3<sup&gt; Tf</sup</em&gt; / J-Maus-Modell von Autismus

Autism Spectrum Disorder (ASD) is a behaviorally defined neurodevelopmental disorder characterized by decreased reciprocal social interaction, abnormal ...

A Novel Procedure for Evaluating the Reinforcing Properties of Tastants in Laboratory Rats: Operant Intraoral Self-administration

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout&#160;or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e.&#160;8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e.&#160;one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets.

The current study evaluates a novel procedure for assessing the reinforcing effects of palatable solutions in laboratory rats: intraoral self-administration. To this end, operant responding (i.e.&#160;lever pressing) for intraoral infusions of sweet solutions at different concentrations was measured on continuous and progressive ratios schedules of reinforcement.

Ein neues Verfahren zur Bewertung der verstärkenden Eigenschaften von Geschmacksstoffe in Labor-Ratten: Operante Intraorale Selbstverwaltung

This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste ...

A Procedure to Observe Context-induced Renewal of Pavlovian-conditioned Alcohol-seeking Behavior in Rats

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate drug-seeking behavior and prompt relapse in abstinent drug users. We have developed a procedure to study the behavioral and neural processes that mediate the impact of context on alcohol-seeking behavior in rats. Following acclimation to the taste and pharmacological effects of 15% ethanol in the home cage, male Long-Evans rats receive Pavlovian discrimination training (PDT) in conditioning chambers. In each daily (Mon-Fri) PDT session, 16 trials each of two different 10 sec auditory conditioned stimuli occur. During one stimulus, the CS+, 0.2 ml of 15% ethanol is delivered into a fluid port for oral consumption. The second stimulus, the CS-, is not paired with ethanol. Across sessions, entries into the fluid port during the CS+ increase, whereas entries during the CS- stabilize at a lower level, indicating that a predictive association between the CS+ and ethanol is acquired. During PDT each chamber is equipped with a specific configuration of visual, olfactory and tactile contextual stimuli. Following PDT, extinction training is conducted in the same chamber that is now equipped with a different configuration of contextual stimuli. The CS+ and CS- are presented as before, but ethanol is withheld, which causes a gradual decline in port entries during the CS+. At test, rats are placed back into the PDT context and presented with the CS+ and CS- as before, but without ethanol. This manipulation triggers a robust and selective increase in the number of port entries made during the alcohol predictive CS+, with no change in responding during the CS-. This effect, referred to as context-induced renewal, illustrates the powerful capacity of contexts associated with alcohol consumption to stimulate alcohol-seeking behavior in response to Pavlovian alcohol cues.

A procedure to study the capacity of an alcohol associated environmental context to trigger the renewal of alcohol-seeking behavior in rats is described.

Eine Vorgehensweise, um Context-induzierte Erneuerung der Pawlowschen Anlage Alkoholsucht bei Ratten Verhalten beobachten

Environmental contexts in which drugs of abuse are consumed can trigger craving, a subjective Pavlovian-conditioned response that can facilitate ...

The Modified Hole Board - Measuring Behavior, Cognition and Social Interaction in Mice and Rats

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure multiple dimensions of unconditioned behavior in small laboratory mammals (e.g., mice, rats, tree shrews and small primates). This paradigm is a valuable alternative for the use of a behavioral test battery, since a broad behavioral spectrum of an animal&#8217;s behavioral profile can be investigated in one single test.
The apparatus consists of a box, representing the &#8216;protected&#8217; area, separated from a group compartment. A board, on which small cylinders are staggered in three lines, is placed in the center of the box, representing the &#8216;unprotected&#8217; area of the set-up. The cognitive abilities of the animals can be measured by baiting some cylinders on the board and measuring the working and reference memory. Other unconditioned behavior, such as activity-related-, anxiety-related- and social behavior, can be observed using this paradigm. Behavioral flexibility and the ability to habituate to a novel environment can additionally be observed by subjecting the animals to multiple trials in the mHB, revealing insight into the animals&#8217; adaptive capacities.
Due to testing order effects in a behavioral test battery, na&#239;ve animals should be used for each individual experiment. By testing multiple behavioral dimensions in a single paradigm and thereby circumventing this issue, the number of experimental animals used is reduced. Furthermore, by avoiding social isolation during testing and without the need to food deprive the animals, the mHB represents a behavioral test system, inducing if any, very low amount of stress.

This protocol describes the modified hole board, which is a behavioral test set-up that comprises the characteristics of an open field and a traditional hole board. This set-up enables the differential analysis of unconditioned behavior of small laboratory mammals as well as the analysis of cognitive abilities.

Der modifizierte Loch Board - Mess Verhalten, Kognition und Sozialinteraktion an Mäusen und Ratten

This protocol describes the modified hole board (mHB), which combines features from a traditional hole board and open field and is designed to measure ...

The Rodent Psychomotor Vigilance Test (rPVT): A Method for Assessing Neurobehavioral Performance in Rats and Mice

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article describes a rodent version of the PVT&#8212;termed the &#34;rPVT&#34;&#8212;that measures similar aspects of attention (i.e., performance accuracy, motor speed, premature responding, and lapses in attention). Data are presented that demonstrate both the short- and long-term usefulness of the rPVT when employed with laboratory rats. Rats easily learn the rPVT, and learning to perform the basic procedure takes less than two weeks of training. Once acquired, rat performances in the rPVT show a high degree of similarity to these same performance measures in the human PVT, including similarities in, lapses in attention, reaction times, vigilance decrements across session time (i.e., the human &#34;time-on-task&#34; effects), and the response-stimulus interval (RSI) effect described for humans. Thus the rPVT can be an extremely valuable tool for assessing the effects of a wide range of variables on sustained attention quite similar to human PVT performances, and thus can be useful for developing novel treatments for neurobehavioral dysfunctions.

The Rodent Psychomotor Vigilance Test rPVT: A Method for Assessing Neurobehavioral Performance in Rats and Mice

A rat version of the human Psychomotor Vigilance Test (PVT) is described that measures aspects of attention similar to those measured with the human PVT, including aspects of human vigilance such as performance accuracy, motor speed, premature responding, and lapses in attention.

Das Nagetier Psychomotorik Vigilance Test (rPVT): Eine Methode zur Beurteilung der Neuropsychologische Leistung bei Ratten und Mäusen

The human Psychomotor Vigilance Test (PVT) is a widely used procedure for measuring changes in fatigue and sustained attention. The present article ...

Reinstatement of Drug-seeking in Mice Using the Conditioned Place Preference Paradigm

The present protocol describes the Conditioned Place Preference (CPP) as a model of relapse in drug addiction. In this model, animals are first trained to acquire a conditioned place preference in a drug-paired compartment, and after the post-conditioning test, they perform several sessions to extinguish the established preference. The CPP permits the evaluation of the conditioned rewarding effects of drugs related to environmental cues. Then, the extinguished CPP can be robustly reinstated by the non-contingent administration of a priming dose of the drug, and by exposure to stressful stimuli. Both methods will be explained here. When the animal reinitiates the behavioral response, a reinstatement of the conditioned reward is considered to have taken place.
The main advantages of this protocol are that it is non-invasive, inexpensive, and simple with good validity criteria. In addition, it allows the study of different environmental manipulations, such as stress or diet, which can modulate relapse into drug seeking behaviors. However, one limitation is that if the researcher aims to explore the motivation and primary reinforcing effects of the drug, it should be complemented with self-administration procedures, as they involve operant responses of animals.

This protocol describes the Conditioned Place Preference (CPP) as a model of relapse. This procedure permits the measurement of relapse in laboratory animals, considering the impact of drug-associated environmental cues as craving and relapse in abstaining addicts is currently the focus of drug-abuse treatment programs.

Wiedereinführung der Drug-seeking bei Mäusen mit dem klimatisierten Ort Präferenz Paradigma

The present protocol describes the Conditioned Place Preference (CPP) as a model of relapse in drug addiction. In this model, animals are first trained to ...

Control of Eating Behavior Using a Novel Feedback System

Subjects eat food from a plate that sits on a scale connected to a computer that records the weight loss of the plate during the meal and makes up a curve of food intake, meal duration and rate of eating modeled by a quadratic equation. The purpose of the method is to change eating behavior by providing visual feedback on the computer screen that the subject can adapt to because her/his own rate of eating appears on the screen during the meal. The data generated by the method is automatically analyzed and fitted to the quadratic equation using a custom made algorithm. The method has the advantage of recording eating behavior objectively and offers the possibility of changing eating behavior both in experiments and in clinical practice. A limitation may be that experimental subjects are affected by the method. The same limitation may be an advantage in clinical practice, as eating behavior is more easily stabilized by the method. A treatment that uses this method has normalized body weight and restored the health of several hundred patients with anorexia nervosa and other eating disorders and has reduced the weight and improved the health of severely overweight patients.

Subjects eat food from a plate placed on a scale connected to a computer that records the weight loss of the plate during the meal. Feedback on the computer screen allows the subject to adapt her/his eating behavior to reference curves thus normalizing body weight.

Kontrolle über das Essverhalten mit einem neuartigen Feedbacksystem

Subjects eat food from a plate that sits on a scale connected to a computer that records the weight loss of the plate during the meal and makes up a curve ...

A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats

A major cause of repeated relapses is a craving for the drug. Drug craving increases progressively during the abstinence period, a phenomenon termed incubation of drug craving. Here, we describe a morphine conditioned place preference (CPP) protocol for measuring the incubation of craving in rats. In this protocol, a CPP paradigm mainly employing somatosensory cues is used to establish a long-term reward memory of morphine. A three-chamber CPP box that differs in the texture of the chamber floor is constructed. First, the animals are tested for their baseline preference to the two side chambers for three consecutive days. Then, they are injected intraperitoneally with morphine/saline and put into their non-preferred/preferred chamber for 45 min. After 6 days of conditioning, their preference to the side chambers is tested for 15 min at different time points after the last conditioning session. With this paradigm, the reward memory of morphine could last for at least 18 days. To test whether the above-mentioned protocol can model increased craving, the number of entrances into the two side chambers are counted during the abstinence period. The results show that the entrances increased, suggesting that the CPP paradigm could mimic the incubation of craving. Future studies can employ this model to study neural mechanisms underlying long-term memory and incubation of craving.

Here, a morphine conditioned place preference (CPP) protocol is described to measure incubation of craving in rats.

Eine konditionierte Ort Präferenz Protokoll zur Messung der Inkubation des Verlangens bei Ratten

A major cause of repeated relapses is a craving for the drug. Drug craving increases progressively during the abstinence period, a phenomenon termed ...