| 其他摘要 | Objectives: 1) In this study, we used a self-made automatic behavior box to explore rodents' seeking behavior of high-value reward (sexual reward) in face of unavoidable foot shock punishment, established a new compulsive reward-seeking behavior model characterized by constantly repetition and regardless of negative consequences, and compared reward-seeking behavior between normal group and drug (morphine) exposure group. 2) We use this model to investigate the individual differences of compulsive level, to evaluate the proportion of rats obsessive-like behaviors in the normal and drug-exposure groups, and to investigate behavioral features of compulsive reward-seeking behaviors. 3) In this study, three behavioral markers (anxiety, reward sensitivity, and novelty seeking) and their changes after drug (morphine) treatment were preliminarily investigated to see if they can predict reward-seeking behavior of rats in the model.
Methods: In this study, a total of 93 adult male Sprague Dawley rats(SD) satisfied the mating screening criterion and underwent three tests (pretest) :the elevated cross maze test, saccharin preference test and novel reactivity test. The morphine group received Binge-like morphine treatment for 5 successive days, while the saline group received only saline injections for five days. On the 6th and 7th day after withdrawal, the elevated cross maze test and saccharine preference test were re-tested, and the behavior box was adapted at the same time. All animals were tested for reward-seeking behavior for 16 consecutive days in the automated behavior box from 8th day since withdrawal, 1 session per day. Each session includes 1 free approach test and 14 restricted approach tests which consists of 7 Punishment trials(P) accompanied by shock and shock light and 7 non-punishment trials (NP) without shock and shock light and the two kinds of trials appeared randomly. The following behavioral indexes were measured and recorded: number of triggered trials, number of completed trials, percentage of completed trials; time spent in zone1, time spent in zone2 and time spent in zone 3; lantency to first entries in zone2 and lantency to first entries in zone3. The compulsion level of animal was measured by the average time spent in zone3 in the last four sessions (Session13-16) in P trials.
Results: 1) The reward-seeking behavior of morphine and saline animals was different: the morphine animals stayed longer in zone2 and shorter in zone3 during baseline period (Session1-3). In Session4-16, the number of trials triggered and completed by morphine animals was significantly lower than that of saline animals, but the percentage of completed trials of morphine animals was higher. Morphine animals were more likely to enter zone3 in which rats might received foot shock. Time spent in zone3 of morphine animals was significantly higher than that of saline animals, while the time spent in zone1 of morphine animals was significantly lowerthan of saline animals. The lantency to first entries in zone3 for morphine animals was significantly lower than that for saline animals. 2) Average time spent in zone3 during last four sessions in P trials was selected as an index reflecting animal’s compulsivity level and the extent to which animals staying in zone3, keeping close to female ras and tolerating electric foot-shock even though they knew there was negative punishment in zone3. According to this index, we distinguished groups of animals with different compulsion phenotypes: Compulsive, Intermediate and Non-Compulsive, and there are stable behavioral differences among 3 compulsion phenotype groups; under the control of pretreatment, session and trial category(P or NP), the partial correlation analysis between this index and other behavioral indexes were performed, and showes that the number of trigger trials, the percentage of trigger trials and time spent in zone3 were positively correlated with the compulsion level, while time spent in Zone1, time spent in zone2 and the the latency to first entries in zone3 were negatively correlated with the level of compulsion. 3) 2 of the 38 saline animals (frequency:5%) and 10 of the 55 morphine animals (frequency:14%) showed compulsive phenotype; Compared with 5%(adjusted probability) in saline animals, morphine animals were more likely to develop compulsive phenotype (adjusted probability:15%). 4) Compulsive level of animals was marginal significantly correlated with anxiety pretest level. There were no differences in pre-test anxiety, reward sensitivity and novel reactivity level among animals with different compulsive phenotypes, and there were no differences in post-test anxiety and reward sensitivity level among animals with different compulsive phenotypes. Compulsive level of animals was not related to anxiety, reward sensitivity and novelty seeking pre-test level, nor related to anxiety and reward sensitivity post-test level.
Conclusion: 1) Compulsive reward-seeking behavior model was established in the self-made automatic box. According to the model, we distinguished 3 subgroups of animals with different compulsion phenotypes; 2) A few saline rats show compulsive tendencies, opioid exposure and withdrawal promotes the occurrence of obsessive-like behaviors in some individuals and increases the proportion of obsessive-compulsive phenotypes; 3) Anxiety, reward sensitivity and novelty-seeking were not associated with the level of compulsion, and no differences between different subgroups of compulsive phenotypes was found. |
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