This paper was supported by CAS Key Laboratory of Mental Health, Institute of Psychology (KLMH2016K01) and Evaluation and Intervention Technology Research for Post-traumatic Stress Patients Population (JCYJ20170413170301569)

This study is approved by the International Review Board (IRB) of the Institute of Psychology, Chinese Academy of Sciences, and all experiments are conducted in accordance with the National Institutes of Health (U.S.A) Guide for Care and Use of Laboratory Animals (2011).
1. Materials and Setup for the Conflict Model
<ol>
	<li>House four rats per cage (50 cm long x 22.5 cm wide x 30 cm high) in colony rooms with controlled temperature (22&#8211;25 &#176;C) and a reversed 12 h/12 h light/dark ...

<ol>
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H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Defining+the+place+of+habit+in+substance+use+disorders.">Defining the place of habit in substance use disorders.</a> Progress in Neuropsychopharmacology &#38; Biological Psychiatry. 87 (Pt A), 22-32 (2018).</li><li>Li, Y., 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=The+consummatory+and+motivational+behaviors+for+natural+rewards+following+long-term+withdrawal+from+morphine:+no+anhedonia+but+persistent+maladaptive+behaviors+for+high-value+rewards.">The consummatory and motivational behaviors for natural rewards following long-term withdrawal from morphine: no anhedonia but persistent maladaptive behaviors for high-value rewards.</a> Psychopharmacology (Berl). 234 (8), 1277-1292 (2017).</li><li>Bai, Y., Belin, D., Zheng, X., Liu, Z., Zhang, Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Acute+stress+worsens+the+deficits+in+appetitive+behaviors+for+social+and+sexual+stimuli+displayed+by+rats+after+long-term+withdrawal+from+morphine.">Acute stress worsens the deficits in appetitive behaviors for social and sexual stimuli displayed by rats after long-term withdrawal from morphine.</a> Psychopharmacology. 234, 1693-1702 (2017).</li><li>Schoenbaum, G., Saddoris, M. 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The inhibitory control deficits caused by drug abuse18 play a key role in promoting compulsive drug seeking/taking behaviors and relapse19,20. The conflict model presented here provides a new approach to explore the changes in inhibitory control of the individuals exposed to addictive drugs.
There are several critical steps in the protocol. First of all, the subjects (male rats) must acquire sexual experience be...

Drug addiction is a chronic brain disease which is characterized by impulsive and compulsive drug seeking and taking1. These key features of addiction have both been hypothesized to result from the impaired ability of inhibitory control2,3, i.e., failing in inhibiting the immediate pursuit of rewarding stimuli and thus developing maladaptive patterns of behavior4.
The go/no-go task and stop-signal task are the prototypical tasks used to measure the ability of response inhibition2,5. These two experimental paradigms assess one&#39;s ability to suppress actions that are inappropriate, by contrasting infrequent inhibitory responses against an implicit go baseline6,7. The response inhibition displayed in these tasks has been shown to be impaired in cocaine users8,9, opiate addicts10, and nicotine users11. Another two tasks&#8212;reversal learning and multiple choice serial reaction time tasks&#8212;also provide measurements of response inhibition/inhibitory control12,13. However, most of these paradigms performed in rodents not only require long-term training so that subjects can distinguish the response requirements represented by different signals, but also the individual differences in learning speed and learning effects may interfere with the results of subsequent inhibitory test11.
In this paper, we present a novel conflict task which can be used to measure the impairment of inhibitory control after exposure to addictive drugs. In this task, a natural rewarding stimulus (sexual stimulus) that represents a high-value reward14, and the aversive stimuli (pins) that male rats have to conquer, are concurrently presented. The male rats have to climb or jump over the obstacle full of pins to approach and investigate the sexual partner. If the animal persists in its approaching behavior regardless of the aversive stimuli, it is considered as a maladaptive or risky reward-seeking behavior. One of the rationales for establishing this task is that it is conceptually simple and does not place heavy demands on executive processes as other tasks do. Compared to other tasks which measure response inhibition, this conflict task is based on natural behavior, and rats with normal sexual function and sexual experience can be tested directly without a learning process. Another rationale is that a conflict presented in this task between approaching the reward and avoiding the aversive stimuli (or the risk of being pricked) may have a better validity, as it mimics what occurs in addicts who often place themselves in the similar conflict but persistently pursue drug reward regardless of the risk of negative consequences in real life15.
Therefore, application of this conflict model is a quick and sensitive way to discover the deficit in inhibitory control after exposure to addictive drugs, or other factors that may influence ability of inhibitory control, such as stress. It also provides a novel behavioral strategy for investigation of neural mechanisms underlying deficits in inhibitory control. Furthermore, alternative modifications can be added onto this task. For example, altering the cost/benefit ratio by replacing the sexual stimulus with the social stimulus can reveal more behavioral significances.

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a conflict model of reward-seeking behavior in male rats

The present protocol describes a novel conflict task as a model of inhibitory control in rats. In this model, a natural rewarding stimulus (sexual stimulus) that represents a high-value reward, and the aversive stimuli (pins), are concurrently presented. The male rats have to climb or jump over the obstacle full of pins to approach and investigate the sexual partner. If the animal persists in their approaching behavior regardless of the aversive stimuli, it is considered as a maladaptive or risky reward-seeking behavior. The conflict task permits the evaluation of deficit in inhibitory control resulting from exposure to abused drug, such as morphine, or a stressful event. 
The main advantage of this model is that it provides a simple and quick way to discover the deficit in inhibitory control after exposure to opiate drugs or other stressful events. In addition to opiates, this behavioral model would also be useful for quickly discovering the inhibitory control deficits induced by other addictive drugs. However, the limitation is that the male rats' performance may be subject to exercising effects with repeated testing under this conflict task. In the future, one can hope that the individuals with the compulsive phenotype of reward-seeking behavior after exposure to opiates will be identified based on modifying this conflict model.

To explore whether this conflict model can reveal maladaptive/risky reward-seeking behavior induced by opiates, the reward-seeking behaviors displayed by the saline- and morphine-pretreated groups were compared by t-tests after short-term (Wd7) and long-term (Wd17) withdrawal from morphine respectively (Figure 2). The results show that on both day 7 and day 17 of withdrawal, the morphine-pretreated rats showed significantly more approaching behaviors than the...

Watch this Scientific Journal Video about A Conflict Model of Reward-seeking Behavior in Male Rats at JoVE.com

A Conflict Model of Reward-seeking Behavior in Male Rats

This conflict model is used to measure the impairment of inhibitory control after exposure to addictive drugs, or other factors that may influence inhibitory control. A sexual stimulus and an aversive obstacle are concurrently presented, thus male rats have to conquer the obstacle to approach the sexual reward.

The present protocol describes a novel conflict task as a model of inhibitory control in rats. In this model, a natural rewarding stimulus (sexual ...

This conflict model can be used for revealing the impairment of inhibitory control after exposure to addictive drugs or other factors that may influence inhibitory control. The main advantage of this model is to provide a simple and a quick way to evaluate the ability of inhibitory control without a learning process. We draw the mastration of this method is critical because the operations in the conflict test are difficult to understand literally.For the confict model, house four rats in each cage for at least 10 days before the tests. Perform all the tests under dim lighting during the dark phase. Prepare 120 milliliters of morphine, 10 milliliters of estradiol benzoate, and 10 milliliters of progesterone for artificial induction of estrus.Handle the ovariectomized female rats at least three times over three days, each time for three minutes before mating screening. About 48 to 52 hours before mating screening or the conflict test, inject the estradiol benzoate at 25 micrograms per rat subcutaneously. Four to six hours before mating screening or the conflict test, subcutaneously inject progesterone at one milligram per rat.To screen the rats for mating performance, place a male rat into the carton with pine wood shaving bedding and let it habituate for five minutes. Next introduce an estrus female rat into the carton and monitor the male copulatory behavior. After the male rat completes its first ejaculation, within 30 minutes or does not display intermission within 15 minutes, transfer the rat back to its home cage.For binge-like morphine treatment, weigh the male rats and calculate the injection volume for each rat based on the body weight. Then inject the rats intraperineally with saline or morphine in a binge-like regimen. After at least six hours, give the rats a second injection in the same way.On the day before testing, transfer the male rat to the conflict test room and allow it to habituate to the open-field reward proximity chamber for 15 minutes. On the testing day, transfer the rat to a chamber allowing free exploration for 10 minutes. Subsequently, place an estrus female rat in the stimulus cage as an incentive and allow the male subject to freely approach it and investigate the incentive rat for five minutes.After five minutes of free approach, transfer the male subject from the stimulus cage to the other end of the arena and place an obstacle. Then start the first trial of the test. Remove the male rat from the stimulus cage about 15 to 20 seconds after each time it surmounts the obstacle.End the trial if the male subject climbs or jumps over the obstacle three times within four minutes. Immediately start the next trial with increasing obstacle difficulty. If a male subject surmounts the obstacle less than three times within four minutes, end the test and record the number of times it surmounts the obstacle.Afterward bring the male rat back to the home cage and scrub the open-field chamber with 05%glacial acetic acid. Score each surmounting and use the sum of the scores for all of the surmountings as a total score for a male subject in this conflict test. To explore whether this conflict model can reveal maladaptive, risky reward-seeking behavior induced by opiates, the reward-seeking behavior is displayed by the saline and morphine pretreated groups were compared after short-term and long-term withdrawal from morphine, respectively.On both day seven and day 17 of withdrawal, the morphine pretreated rats showed significantly more approaching behaviors than the saline pretreated rats, suggesting that the morphine withdrawn rats displayed more perseverative behaviors upon aversive obstacle, and this maladaptive behavior persists for a long time after withdrawal. The repeated test showed a significant main effect of pretreatment. The correlation of the scores between day seven and day 14 of withdrawal, showed that the rats'reward-seeking behaviors were roughly stable over repeated tests.To investigate the influence of stressful events on the ability of inhibitory control in animals, the drug naive rats were exposed to an intermittent foot-shock stress before the conflict test. Although there was no significant difference between the stress and control groups, the reward-seeking behaviors displayed a bimodal distribution within the stress group, suggesting the markedly differential effects of acute stress on risky reward-seeking behaviors among individuals. It's important that male rats to acquire sexual experience before entering follow-up conflict tasks.And the stress factors should be tightly controlled throughout the experiment. In this conflict task, one can also investigate the impact of rewards value on reward-seeking behaviors. For example, changing some reward value by replacing the female rat with a male rat.Don't forget that estrogen benzoate and progesterone are harmful to humans, so wear masks and gloves all the time when in contact with them.

a-conflict-model-of-reward-seeking-behavior-in-male-rats

Research

JoVE Journal

Behavior

7.3K visualizações.  Chinese Academy of Sciences. Este modelo de conflito pode ser usado para revelar o comprometimento do controle inibitório após a exposição a drogas viciantes ou outros fatores que podem influenciar o controle inibitório. A principal vantagem deste modelo é fornecer uma maneira simples e rápida de avaliar a capacidade de controle inibitório sem um processo de aprendizagem. Desenhamos a mastração deste método é fundamental porque as operações no teste de conflito são difíceis de entender literalmente.