Os autores gostariam de reconhecer financiamento UL1TR000071 (NCATS), P30DK079638 (NIDDK), P30DA028821 (NIDA) e T32DA07287 (NIDA).

Todos os procedimentos experimentais estão de acordo com o Guia para o (Institute of Laboratory Animal Resources (EUA), 1996) Cuidado e Uso de Animais de Laboratório e com a aprovação do Comitê Animal Care Institucional e Use na Universidade do Texas Medical Branch. 1. Assuntos <ol><li> Única casa ratos machos Sprague-Dawley pesando 225-250 g a 21 ° C e 30-50% de humidade relativa, com um ciclo de luz-escuro de 12 horas (luzes acesas 06:00-6: 00). </li><li> Manter ratos em um alimento de baixa gordura (10% de gordura, energia). Habituar ratos para alimentos e colónia ambiente durante pelo menos 7 dias antes da experimentação. Animais estão habituados ao manuseio e dosagem de veículo por três dias antes de iniciar os estudos. No primeiro dia após a habituação é o Dia experimental 1. </li></ol> 2. Preferências de linha de base <ol><li> Dia 1, encher dois alimentadores limpo, um marcado com um A e B com o outro, com 10% de gordura de alimentos para cada gaiola. Weigh os funis de alimentos (com alimentos) e colocá-los na gaiola, garantindo o rato tem acesso a ambos. </li><li> Dia 2, aproximadamente ao mesmo tempo alimentadores foram colocados na gaiola no dia anterior, registrar os pesos da tremonha de alimentação e mudar as posições da tremonha A e B. Esta tremonha atenua viés posição. Sempre examinar a gaiola para qualquer alimento removido do funil, pesá-lo e explicá-la. A ingestão de alimentos é medido pela mudança no peso funil entre os dias. </li><li> Dia 3, registra os pesos funil de alimentos como antes. Examine a quantidade de alimentos consumidos em cada posição comedouro e identificação comedouro (A e B). Estes dados dão um entendimento básico de viés posição e preferência funil específico, e deve ter uma pontuação de preferência de cerca de 50% indicando que não há preferência. Jogue fora a comida restante. </li></ol> 3. Fat Preferências <ol><li> Dia 3, obter dois funis de alimentos limpos para cada gaiola. É importante a utilização de alimentadores limpassempre que alternar entre os diferentes alimentos para evitar confusão perfumes a partir de experiências anteriores. Preencha funil A, com 12,5% de gordura e alimentos hopper B com alimentos de gordura de 15% (Tabela 1). Anote os pesos de partida de cada funil e coloque ambos na gaiola. </li><li> Dia 4, registrar os pesos de cada funil, alternando as posições de hopper A e B funil em cima de colocá-los de volta na gaiola. </li><li> Dia 5, registrar os pesos de cada funil. Depois de determinar a massa de cada alimento consumido em ambos os dias, de preferência de alimentos do rato pode ser determinada. </li><li> Repita os passos 3.1 a 3.3 várias vezes com os mesmos animais, utilizando 12,5% de gordura de alimentos, em comparação com os alimentos, com o aumento do teor de gordura (por exemplo, em primeiro lugar 15%, próximo de 17,5%, depois 20% e, finalmente, 45% de gordura). </li></ol> 4. Cálculos e Análise de Dados <ol><li> Calcula-se a ingestão diária de alimentos para cada animal, subtraindo a massa final do comedouro + a partir da massa inicial do alimento+ Funil. Como cada alimento é medido ao longo de 2 dias, 2 dias de total pode ser somados para cada teor de gordura%. </li><li> Calcule a pontuação preferência gordura dividindo a ingestão de alimentos de gordura maior do total de alimentos consumidos durante cada período de dois dias. Por exemplo, uma ratazana comeram 8,9 g de dieta de gordura de 12,5% e 27,5 g de dieta de 17,5% ao longo de 2 dias. Portanto, a pontuação de preferência para que cada animal é de 76% (27,5 dividido por 36,4). </li><li> Média e do gráfico da contagem de preferência para cada dieta (15%, 17,5%, 20%, e 45% de gordura) (Figura 3). A ingestão total de alimento também é informativa e pode facilmente ser representados como gramas (Figura 4). </li><li> Expressam o marcador de preferência (Figura 5A) e da ingestão de alimentos totais (Figura 5B) como uma função do consumo total de energia (kcal), utilizando a densidade de energia na Tabela 1. </li><li> Se usar mais do que um grupo de animais, realizar uma de duas vias de repetiçãoed mede ANOVA seguido de um pós-teste de Bonferroni. A análise de energia indica que n = 8 animais por grupo é adequado para a detecção de uma diferença de 7% entre os grupos de tratamento. </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>

Os autores não têm nada a revelar.

O modelo de Preferências Fat é um ensaio informativo e fácil de realizar do comportamento alimentar. Este ensaio oferece uma oportunidade para identificar neural e mecanismos moleculares subjacentes preferência alimentar, que é uma importante área ainda pouco estudado de pesquisa da obesidade. Alterações na preferência de gordura a partir de diferenças genéticas ou manipulações farmacológicas podem ser visualizadas como desvios para a direita ou para a esquerda na curva de preferência (Figura 3B)....

A obesidade é um problema prevalente nos Estados Unidos 1, com os Centros de Controle e Prevenção de Doenças estimam que mais de um terço dos adultos americanos são obesos. A obesidade também tem sido identificada como um fator de risco para inúmeras preocupações com a saúde, incluindo diabetes tipo 2, pressão alta e colesterol alto 2. Embora muitos fatores têm sido mostrados para influenciar o aumento das taxas de obesidade, há um interesse contínuo e controvérsia no papel macronutrientes jogar na obesidade 3,4. Um fator que contribui para a obesidade é alta ingestão de gordura 5. O aumento de gordura na dieta está relacionada com o aumento do consumo de energia humano 6 e aumentos significativos no conteúdo de gordura corporal 7,8. Além disso, a gordura dietética tem valor de recompensa durante e após o consumo de 7,9. Portanto, determinar quais os fatores que influenciam a preferência por alimentos ricos em gordura pode tanto guia farmacoterapêuticas design e promover a compreensão das escolhas alimentares subjacentes que podem levar à obesidade. O modelo de Preferências Fat descrito aqui testa para a preferência dos ratos entre alimentos de diferentes teor de gordura, mas o valor nutricional semelhante. Especificamente, este modelo apresenta os ratos com uma escolha de dois alimentos diferentes ao mesmo tempo, permitindo, assim, a quantificação de preferência baseada em gramas consumidas dos alimentos gordura menor versos a comida de gordura superior. Os efeitos farmacológicos e genéticas pode ser medida como uma mudança na preferência por alimentos com alto teor de gordura. O modelo de preferência gordura serve para complementar os modelos de ingestão de alimentos saborosos amplamente utilizados 10, mas também oferece várias vantagens. Este modelo permite que o experimentador para avaliar especificamente o comportamento de alimentação em um ambiente controlado no qual duas opções de alimentos estão disponíveis. Os modelos tradicionais de alimentação rica em gordura só oferecer um alimento que elimina a capacidade de estudar a escolha dos alimentos, uma importante quantopecto da ingestão alimentar humana. Alguns ensaios oferecem vários tipos de alimentos e são muitas vezes referida como &quot;cafeteria&quot; estudos tipo de alimentação 11. Estes estudos sofrem de reprodutibilidade porque a alimentação humana é muitas vezes utilizado no ensaio e não é bem adequado ao ambiente do laboratório devido à variabilidade de nutrientes. Usamos dietas definidos que contêm ingredientes purificados individuais melhorando em muito a reprodutibilidade e flexibilidade para alterar o conteúdo de macronutrientes como a gordura da dieta. Com ingestão de gordura mais elevado associado com a obesidade em humanos 5 e a preferência humana natural para alimentos gordos maiores de 12, os tratamentos que alteram preferência rato para alimentos ricos em gordura podem fornecer informações valiosas sobre a obesidade.

<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

A obesidade é um problema crescente nos Estados Unidos da América, com mais do que um terço da população classificada como obesos. Um factor que contribui para este distúrbio multifatorial é o consumo de uma dieta rica em gordura, um comportamento que tenha sido demonstrado que o aumento tanto da ingestão calórica e teor de gordura corporal. No entanto, os elementos que regulam a preferência por alimentos ricos em gordura em relação a outros alimentos permanecem escassos. Para superar esse déficit, um modelo de forma rápida e facilmente testar mudanças na preferência por gordura na dieta foi desenvolvida. O modelo de preferência de gordura apresenta ratos com uma série de escolhas entre alimentos com diferentes conteúdos de gordura. Como seres humanos, os ratos têm um viés natural para consumir alimentos ricos em gordura, tornando o modelo de rato ideal para estudos translacionais. Mudanças na preferência pode ser atribuído ao efeito de qualquer diferenças genéticas ou farmacológicas. Este modelo permite a exploração de determinantes de preferência gordura e screening agentes farmacoterapêuticos que a aquisição influência da obesidade.

Os ratos tiveram acesso físico para ambos os alimentadores simultaneamente (Figura 1), a fim de demonstrar a preferência para as escolhas alimentares disponíveis com diferentes matérias gordas (Tabela 1). Rat comida foi pesada diariamente e qualquer derrame comida foi facilmente encontrados e contabilizados (Figura 2). Derramamento de partículas de alimentos finos foi encontrado para ser mínima e não influenciar substancialmente os dados. Usando o modelo de Prefe...

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

Influências de conteúdo de gordura da dieta, tanto o consumo de energia e composição de gordura corporal em mamíferos. Ao examinar a preferência dos ratos por alimentos ricos em gordura em uma série de experimentos de escolha, é possível testar diferenças genéticas e intervenções farmacológicas sobre sua preferência por alimentos ricos em gordura.

Preferência de Gordura: Um Modelo Novel de comportamento alimentar em ratos

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 visualizações.  University of Texas Medical Branch.  Influências de conteúdo de gordura da dieta, tanto o consumo de energia e composição de gordura corporal em mamíferos. Ao examinar a preferência dos ratos por alimentos ricos em gordura em uma série de experimentos de escolha, é possível testar diferenças genéticas e intervenções farmacológicas sobre sua preferência por alimentos ricos em gordura. 

Vídeo: 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.

Microinjeção estereotáxica de vetores virais Expressando Cre Recombinase para estudar o papel de genes alvo em cocaína condicionado Lugar de Preferência

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

Comportamento

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.

Um procedimento para estudar o efeito da restrição alimentar prolongada em heroína Buscando em ratos abstinentes

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 Estereotipia no BTBR<em&gt; T<sup&gt; +</sup&gt; Itpr3<sup&gt; Tf</sup</em&gt; / J Rato modelo de autismo

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.

Um novo procedimento para avaliar as propriedades de reforço de Tastants em laboratório ratos: Intraoral auto-administração operante

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.

Um procedimento para Observar Renovação induzida por Contexto de pavloviano condicionado Comportamento Álcool-seeking em Ratos

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.

The Hole Board Modificado - Medir Comportamento, Cognição e Interação Social em camundongos e ratos

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.

O psicomotora Teste Rodent Vigilância (rPVT): um método para avaliar Neurobehavioral Desempenho em ratos e camundongos

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

Detecting Behavioral Deficits in Rats After Traumatic Brain Injury

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, few studies have investigated the long-term effects of injury in rodent models of TBI. Shown here are behavioral measures that are well-established in TBI research for times early after injury, such as two weeks, until two months. Some of these methods have previously been used at later times after injury, up to one year, but by very few laboratories. The methods demonstrated here are a short neurological assessment to test reflexes, a Beam-Balance to test balance, a Beam-Walk to test balance and motor coordination, and a working memory version of the Morris water maze that can be sensitive to deficits in reference memory. Male rats were handled and pre-trained to neurological, balance, and motor coordination tests prior to receiving parasagittal fluid percussion injury (FPI) or sham injury. Rats can be tested on the short neurological assessment (neuroscore), the beam-balance, and the Beam-Walk multiple times, while testing on the water maze can only be done once. This difference is because rats can remember the task, thus confounding the results if repeated testing is attempted in the same animal. When testing from one to three days after injury, significant differences are detected in all three non-cognitive tasks. However, differences in the Beam-Walk task were not detectable at later time points (after 3 months). Deficits were detected at 3 months in the Beam-Balance and at 6 months in the neuroscore. Deficits in working memory were detected out to 12 months after injury, and a deficit in a reference memory first appeared at 12 months. Thus, standard behavioral tests can be useful measures of persistent behavioral deficits after FPI.

The goal of the behavioral tests presented here is to detect functional deficits in rats after traumatic brain injury. Four specific tests are presented that detect deficits in behaviors to reflect the damage to specific brain areas at times extending to one year after injury.

Detecção de défices comportamentais em ratos após lesão cerebral traumática

With the increasing incidence of traumatic brain injury (TBI) in both civilian and military populations, TBI is now considered a chronic disease; however, ...

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.

Reintegração de busca de drogas em ratos utilizando o paradigma de preferência lugar condicionado

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.

Controle de comer comportamento usando um sistema de Feedback de romance

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 ...