Name: a procedure to study the effect of prolonged food restriction on heroin seeking in abstinent rats
Uploaded: 2013-11-11T20:00:00
Description: Watch this Scientific Journal Video about A Procedure to Study the Effect of Prolonged Food Restriction on Heroin Seeking in Abstinent Rats at JoVE.com

This work was supported by the Natural Sciences &#38; Engineering Council Discovery Program (US: 298915), the Fonds de Recherche du Quebec - Sant&#233; (CSBN), and the Canada Research Chairs Program (US).

1. Animals
All rats are treated in accordance with the guidelines of the Canadian Council on Animal Care and approval for all the experimental procedures was granted by the Concordia University Animal Research Ethics Committee.
<ol>
	<li>Obtain rats at 275-300 g (males) or 225-250 g (females). House rats in pairs until surgery in standard plastic cages containing corncob bedding and shredded paper.</li>
	<li>Maintain rats on a reversed light-dark cycle (light off at 9:30 AM).</li>
	<li>Make ...

<ol>
	<li>Jaffe, J. H., Gilman, A. G., Rall, T. W., Nies, A. S., Taylor, P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Drug+addiction+and+drug+abuse.">Drug addiction and drug abuse.</a> Goodman &amp; Gilman's the pharmacological basis of therapeutics. , 522-573 (1990).</li><li>O'Brien, C. P., McLellan, A. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Myths+about+the+treatment+of+addiction.">Myths about the treatment of addiction.</a> Lancet. 347, 237-240 (1996).</li><li>Childress, A. R., Ehrman, R., Rohsenow, D. J., Robbins, S. J., O'Brien, C. P., Lowinson, J. W., Luiz, P., Millman, R. B., Langard, G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Classically+conditioned+factors+in+drug+dependence.">Classically conditioned factors in drug dependence.</a> Substance abuse: A comprehensive textbook. , 56-69 (1992).</li><li>Sinha, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=How+does+stress+increase+risk+of+drug+abuse+and+relapse?.">How does stress increase risk of drug abuse and relapse?.</a> Psychopharmacology. 158, 343-359 (2001).</li><li>Cheskin, L. J., Hess, J. M., Henningfield, J., Gorelick, D. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Calorie+restriction+increases+cigarette+use+in+adult+smokers.">Calorie restriction increases cigarette use in adult smokers.</a> Psychopharmacology. 179, 430-436 (2005).</li><li>Krahn, D., Kurth, C., Demitrack, M., Drewnowski, 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+relationship+of+dieting+severity+and+bulimic+behaviors+to+alcohol+and+other+drug+use+in+young+women.">The relationship of dieting severity and bulimic behaviors to alcohol and other drug use in young women.</a> J. Subst. Abuse. 4, 341-353 (1992).</li><li>de Wit, H., 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>Shaham, Y., Shalev, U., Lu, L., De Wit, H., 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=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, 3-20 (2003).</li><li>Shalev, U., Highfield, D., Yap, J., Shaham, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=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. 150, 337-346 (2000).</li><li>Tobin, S., Newman, A. H., Quinn, T., 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=A+role+for+dopamine+D1-like+receptors+in+acute+food+deprivation-induced+reinstatement+of+heroin+seeking+in+rats.">A role for dopamine D1-like receptors in acute food deprivation-induced reinstatement of heroin seeking in rats.</a> Int. J. Neuropsychopharmacol. 12, 217-226 (2009).</li><li>Katz, J. L., Higgins, S. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+validity+of+the+reinstatement+model+of+craving+and+relapse+to+drug+use.">The validity of the reinstatement model of craving and relapse to drug use.</a> Psychopharmacology. 168, 21-30 (2003).</li><li>Epstein, D. H., Preston, K. L., Stewart, J., Shaham, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Toward+a+model+of+drug+relapse:+an+assessment+of+the+validity+of+the+reinstatement+procedure.">Toward a model of drug relapse: an assessment of the validity of the reinstatement procedure.</a> Psychopharmacology. 189, 1-16 (2006).</li><li>Zacny, J. P., 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=The+effects+of+a+restricted+feeding+regimen+on+cigarette+smoking+in+humans.">The effects of a restricted feeding regimen on cigarette smoking in humans.</a> Addict. Behav. 17, 149-157 (1992).</li><li>Fuchs, R. A., Lasseter, H. C., Ramirez, D. R., Xie, X. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Relapse+to+drug+seeking+following+prolonged+abstinence:+the+role+of+environmental+stimuli.+Drug+Discov.+Today+Dis.">Relapse to drug seeking following prolonged abstinence: the role of environmental stimuli. Drug Discov. Today Dis.</a> Models. 5, 251-258 (2008).</li><li>D'Cunha, T. M., Sedki, F., Macri, J., Casola, C., 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=The+effects+of+chronic+food+restriction+on+cue-induced+heroin+seeking+in+abstinent+male+rats.">The effects of chronic food restriction on cue-induced heroin seeking in abstinent male rats.</a> Psychopharmacology. 225, 241-250 (2013).</li><li>Caprioli, D., Celentano, M., Dubla, A., Lucantonio, F., Nencini, P., Badiani, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ambience+and+drug+choice:+cocaine-+and+heroin-taking+as+a+function+of+environmental+context+in+humans+and+rats.">Ambience and drug choice: cocaine- and heroin-taking as a function of environmental context in humans and rats.</a> Biol. Psychiatry. 65, 893-899 (2009).</li></ol>

The procedure described here has strong face validity because 1) it allows for voluntary drug intake and control over drug administration, 2) it uses a route of administration that is common in human addicts, 3) it reflects (relatively) prolonged periods of drug exposure and abstinence, and 4) it avoids the extinction training before the drug-seeking test that is integral to the reinstatement procedure but is rarely observed in human addicts14. In addition, the procedure models a prolonged food restriction con...

One of the major difficulties in the treatment of drug addiction is the high rate of relapse, even after prolonged periods of abstinence1,2. Studies in human addicts have identified a critical contribution of environmental challenges, such as the exposure to drug-associated discrete cues or environments3 and stressful life events4, to relapse. A common environmental challenge that was found to have an effect on drug taking and craving is chronic food restriction. For example, it has been reported that chronic caloric restriction is associated with increased cigarette smoking5.&#160;Furthermore,&#160;dieting severity (caloric restriction) is positively correlated with an increased prevalence of drug use in young women6. However, the underlying brain mechanisms are not fully understood.
Due to practical and ethical considerations related to human research, animal models have been developed to identify the relevant neural mechanisms. We have previously used the reinstatement procedure7,8 to demonstrate resumption of extinguished drug seeking in rats that are exposed to acute (24-48 hr) food deprivation9,10. However, an integral part of the reinstatement procedure is an extinction period that is not a common feature of drug addiction treatments11 (but see Epstein et al.12 for a comprehensive discussion on the validity of the reinstatement procedure). Moreover, in the particular case of dietary manipulations in humans, only chronic food restriction, but not acute food deprivation, was shown to effectively increase drug-taking5,13.
Consequently, we have suggested an &#34;abstinence procedure&#34;14 that allows the study of the effects of chronic food restriction on drug seeking. Using this procedure we have recently demonstrated a robust augmentation of heroin seeking in abstinent rats following exposure to 14 days of mild food restriction15.

<table border="0" cellpadding="0" cellspacing="0" width="840">
	<colgroup>
		<col />
		<col />
		<col />
	</colgroup>
	<tbody>
		<tr height="69">
			<td height="69" style="height:69px;width:177px;">Name</td>
			<td style="width:411px;">Company</td>
			<td style="width:252px;">Catalogue Number</td>
		</tr>
		<tr height="103">
			<td height="103" style="height:103px;width:177px;">Ketamine (Vetalar, 100 mg/ml)</td>
			<td style="width:411px;">Bioniche Animal Health</td>
			<td style="width:252px;">Obtained through local distributer</td>
		</tr>
		<tr height="103">
			<td height="103" style="height:103px;width:177px;">Xylazine (Rompun, 100 mg/ml)</td>
			<td style="width:411px;">Bayer</td>
			<td style="width:252px;">Obtained through local distributer</td>
		</tr>
		<tr height="111">
			<td height="111" style="height:111px;width:177px;">Heroin HCl</td>
			<td style="width:411px;">National Institute for Drug Abuse, Research Triangle Park, NC, USA</td>
			<td style="width:252px;"></td>
		</tr>
		<tr height="137">
			<td height="137" style="height:137px;width:177px;">Anafen injection 1 mg/ml Vial/20 ml</td>
			<td style="width:411px;">CDMV, Canada</td>
			<td align="right" style="width:252px;">12868</td>
		</tr>
		<tr height="20">
			<td height="20" style="height:20px;"></td>
			<td></td>
			<td></td>
		</tr>
		<tr height="35">
			<td height="35" style="height:35px;">Equipment</td>
			<td></td>
			<td></td>
		</tr>
		<tr height="69">
			<td height="69" style="height:69px;width:177px;">Name</td>
			<td style="width:411px;">Company</td>
			<td style="width:252px;">Catalogue Number</td>
		</tr>
		<tr height="137">
			<td height="137" style="height:137px;width:177px;">Silastic tubing (ID 0.02, OD 0.037)</td>
			<td style="width:411px;">Fisher Scientific</td>
			<td style="width:252px;">1118915A</td>
		</tr>
		<tr height="69">
			<td height="69" style="height:69px;width:177px;">GE marine silicon</td>
			<td style="width:411px;">GE</td>
			<td style="width:252px;">SE-1134</td>
		</tr>
		<tr height="137">
			<td height="137" style="height:137px;width:177px;">Tygon tubing (ID 0.02, OD 0.060)</td>
			<td style="width:411px;">VWR</td>
			<td style="width:252px;">63018-044</td>
		</tr>
		<tr height="69">
			<td height="69" style="height:69px;width:177px;">Cannulae (22 G, 5-up)</td>
			<td style="width:411px;">Plastics One</td>
			<td style="width:252px;">C313G-5up</td>
		</tr>
		<tr height="103">
			<td height="103" style="height:103px;width:177px;">Liquid swivels, plastic, 22 G</td>
			<td style="width:411px;">Lomir Biomedical, Inc.</td>
			<td style="width:252px;">RSP1</td>
		</tr>
		<tr height="137">
			<td height="137" style="height:137px;width:177px;">Fixed speed infusion pump (3.3 rpm)</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">A73-01-3.3</td>
		</tr>
		<tr height="69">
			<td height="69" style="height:69px;width:177px;">Rat test cage</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">H10-11R-TC</td>
		</tr>
		<tr height="103">
			<td height="103" style="height:103px;width:177px;">Stainless steal grid floor</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">H10-11R-TC-SF</td>
		</tr>
		<tr height="69">
			<td height="69" style="height:69px;width:177px;">House light-rat</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">H11-01R</td>
		</tr>
		<tr height="103">
			<td height="103" style="height:103px;width:177px;">Single high-bright cue-rat</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">H11-03R</td>
		</tr>
		<tr height="103">
			<td height="103" style="height:103px;width:177px;">Tone module 2.9 kHz</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">H12-02R-2.9</td>
		</tr>
		<tr height="69">
			<td height="69" style="height:69px;width:177px;">Retractable lever-rat</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">H23-17RA</td>
		</tr>
		<tr height="35">
			<td height="35" style="height:35px;width:177px;">Balance arm</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">H29-01</td>
		</tr>
		<tr height="103">
			<td height="103" style="height:103px;width:177px;">Sound attenuation boxes</td>
			<td style="width:411px;">Concordia University</td>
			<td style="width:252px;">Home made</td>
		</tr>
		<tr height="69">
			<td height="69" style="height:69px;width:177px;">System controller 2</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">SYS CTRL 2</td>
		</tr>
		<tr height="69">
			<td height="69" style="height:69px;width:177px;">System power base</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">H01-01</td>
		</tr>
		<tr height="103">
			<td height="103" style="height:103px;width:177px;">Habitest Universal Linc</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">H02-08</td>
		</tr>
		<tr height="137">
			<td height="137" style="height:137px;width:177px;">Environment connection board &#38; Linc cable</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">H03-04</td>
		</tr>
		<tr height="103">
			<td height="103" style="height:103px;width:177px;">Graphic State Notation 3</td>
			<td style="width:411px;">Coulbourn Instruments</td>
			<td style="width:252px;">GS3</td>
		</tr>
	</tbody>
</table>

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.

Body weights over time: Typical results demonstrate that body weights remain stable throughout heroin self-administration training. During abstinence, rats with unrestricted access to chow increase their body weight, while those that are food restricted decrease their body weight to approximately 90% of their own original body weight or 75-80% of the sated rats&#39; body weight (Figure 2).
Infusions, active and inactive lever responses over training: Infusions an...

Watch this Scientific Journal Video about A Procedure to Study the Effect of Prolonged Food Restriction on Heroin Seeking in Abstinent Rats at JoVE.com

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

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.

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

Research

JoVE Journal

Behavior

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 ...

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 ...

A Treatment Package without Escape Extinction to Address Food Selectivity

Feeding difficulties and feeding disorders are a commonly occurring problem for young children, particularly children with developmental delays including ...

A Method for Evaluating the Reinforcing Properties of Ethanol in Rats without Water Deprivation, Saccharin Fading or Extended Access Training

Operant oral self-administration methods are commonly used to study the reinforcing properties of ethanol in animals. However, the standard methods ...

Feeding Experimentation Device (FED): Construction and Validation of an Open-source Device for Measuring Food Intake in Rodents

Feeding Experimentation Device FED: Construction and Validation of an Open-source Device for Measuring Food Intake in Rodents

Food intake measurements are essential for many research studies. Here, we provide a detailed description of a novel solution for measuring food intake in ...

A Method to Test the Effect of Environmental Cues on Mating Behavior in Drosophila melanogaster

A Method to Test the Effect of Environmental Cues on Mating Behavior in Drosophila melanogaster

An individual's sexual drive is influenced by genotype, experience and environmental conditions. How these factors interact to modulate sexual behaviors ...

Combining Quantitative Food-intake Assays and Forcibly Activating Neurons to Study Appetite in Drosophila

Combining Quantitative Food-intake Assays and Forcibly Activating Neurons to Study Appetite in Drosophila

Food consumption is under the tight control of the brain, which integrates the physiological status, palatability, and nutritional contents of the food, ...

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 ...

Tickling, a Technique for Inducing Positive Affect When Handling Rats

Handling small animals such as rats can lead to several adverse effects. These include the fear of humans, resistance to handling, increased injury risk ...