| Objective: To observe whether chronic stress can promote progress of food addiction or not and to explore possible mechanisms involved.Method: Firstly,32 mice were randomly divided into control group,High-fat food group(HF),light stress group(LG),High-fat food and light stress group(HFLG)co-inducing group.They were given corresponding treatment on 6:00pm-8:00pm for one month.Then feeding behaviors and anxiety behaviors,body weight were tested for each group.According to these behaviors,food addiction-like score was evaluated.CRFR1,Dopr1,Dopr2 m RNA of nucleus accumbens of four groups mice were detected by q PCR after they were sacrificed.Secondly,30 mice were randomly divided into control group,Sh-RNA group,overexpress group.AAV-NC,AAV-Sh CRFR1,AAV-CRFR1 were respectively injected into their nucleus accumbens in the groups above.After 1 month model inducing,feeding behaviors and anxiety behaviors were tested.QPCR were also used to detect changes of CRFR1,Dopr1,Dopr2 m RNA in nucleus accumbens for each group.Result: In the first part of the experiment,mice in the HF group and co-inducing group had gradually increased 2 hours of food intake and 24 hours of food intake compared with the control group after one month of induction,and the food intake after fasting increased significantly.Complusive eating intake of mice in the co-inducing group was significantly higher than the control group and high-fat group.Time in the central area in the open field test was significantly decreased in the mice of light stress group and co-inducing group.Compared with the control group,mice in co-inducing group spent less time in the open arm in the elevated plus-maze test and less time in white boxes in the black-and-white box shuttle test.They also had less food addiction-like score and increase rate of body weight when comparing with the control group and the HF group.Our q PCR test revealed that expression of Dopr2 and CRFR1 in the nucleus accumbens of mice in the co-inducing group significantly increased.In the second part of our research,it was found that mice had higher 2-hour and 24-hour food intake when CRFR1 in nucleus accumbens over-expressed after infection with AAV-CRFR1.Their motivation for high-fat foods was also heightened.In addition,they spent less time in the open arm in the elevated plus-maze test and less time in the central area in the open field test and less time in the white box in the black-and-white box shuttle experiment.The overexpression group had higher food addiction-like score and body weight increase rate.On the contrary,after CRFR1 in the nucleus accumbens was knockout,mice in the knockout group decreased their food intake volume,motivation for eat high-fat foods and food intake volume after fasting,and ameliorated complusive eating.Thus their food addiction-like score and body weight increase rate significantly decreased.QPCR results showed that dopamine D2 receptor m RNA upregulated after overexpressing CRFR1 in nucleus accumbens whereas downregulated after CRFR1 in nucleus accumbens knockouted.Dopr1 m RNA expression had no significant changes.Conclusion: Chronic stress can promote the progress of food addiction;possible machanism involved may be associated with upregulation Crfr1 and dopr2 in the nucleus accumbens. |