| Part one: High-frequency Deep Brain Stimulation BilateralAccumbens in Rats and Its Effect on Addictive Behavior(ONE)High-Frequency Deep Brain Stimulation Bilateral Accumbens During Extinctive Phase in Rats and Its Effect on Addictive BehaviorObjective: To investigate the influence of deep brain stimulation(DBS)at high frequency to the bilateral nucleus accumbens on morphine-induced conditioned place preference(CPP)and relapse behaviors during extinction phase among the morphine-dependent ratsMethods:Twenty adult SD rats weighing 280g-300 g were used in the experiment.Through stereotactic operation,outer electrode cannula was implanted into rats’ bilateral nucleus accumbens.After 5 days of rest,the morphine-dependent rat model with CCP was established through intraperitoneal morphine injection(10mg/kg).The rats,after being divided randomly into experimental group(morphine + DBS)and control group(morphine + sham DBS),were electrically stimulated using modified DBS circuits.Rats in the experimental group was given high frequency electrical stimulations(parameters: frequency 120 Hz,wave length 60 ms,intensity 0.3 m A,time 30 min/d).Control group was sham stimulation group.The CCP score of the two groups were recorded the day after stimulation until successful extinction and then the extinction time between the two groups was compared.Twenty four hours after extinction,rats of the two groups were given small dose of morphine(3mg/kg)to trigger relapse.Meanwhile,the CCP score was recorded and compared between the two groups.Results:1.After rats CPP paradigm establishment,rats spent(603.2s ± 80.80s)in the drug-paired chamber significantly longer than that before model establishment(371.1s±60.84s)(p<0.0001),which indicated that the modeling was a success.2.In the experimental group the average extinction duration was 26 days while in the control group the time was 6 days.In contrast with the control group,it was evident that the experimental group had a longer extinction time.3.After successful extinction the rats were given small dose of morphine to trigger relapse within 24 h.In the experimental group,the retention time within the drug-paired chamber was 357.01 s ± 192.72 s while in the control group the during was 704.91 ± 181.35 s.In contrast with the control group,it was evident that the experimental group had a shorter retention time(p=0.0346).Conclusion:High frequency DBS to rats’ bilateral nucleus accumbens can prolong extinction time but inhibit relapse behavior.(TWO)High-Frequency Deep Brain Stimulation in Rats Bilateral Accumbens During Abstinence Period and Its Effect on Relapse BehaviorObjective: To investigate the influence of deep brain stimulation(DBS)at high frequency to the bilateral nucleus accumbens on morphine-induced conditioned place preference(CPP)and relapse behaviors during abstinence phase among the morphine-dependent ratsMethods :Twenty adult SD rats,weighted 280g-300 g,electrode casing pipe was implanted into rats bilateral nucleus accumbens by stereotactic surgery,postoperative rest for 5d,Intraperitoneal injection of morphine(10 mg/kg)induced rats to form conditioned position preference model.paired extinctive method was applied during extinguish process.Rats were randomly divided into experimental group(morphine+DBS)and control group(morphine+false)after successful extinction.Improving DBS system was used for electrical stimulation,the experimental group was given high frequency electrical stimulation(stimulation parameters: 120 HZ frequency,pulse width 60 ms,stimulation intensity of 0.3 m A,exciting time 30 min/d),control group set to false.continuous stimulation for 7 days.Small doses of morphine to induce relapse within 24 h after last stimulation,then test CCP score and compared between groups.Result:1 、 After rats CPP paradigm establishment,rats spent(616.2s±74.69s)in the drug-paired chamber significantly longer than that before model establishment(353.9s±84.33s)(p<0.0001),which indicated that the modeling was a success.2、The CPP score after extinction shows 456.4s±148.8s,which show significant statistical difference compare to pre-conditioned CPP score 616.2s±74.69s(P=0.0219).Meanwhile have no significant statistical difference compare to post-conditioned CPP score 353.9s±84.33 s,which indicated successful extinction。3、Small doses of morphine induce relapse within 24 h after extinction,In the experimental group,the retention time within the drug-paired chamber was(330.1 s±212.6 s)while in the control group the during was(684.2s±230.2s).In contrast with the control group,it was evident that the experimental group had a shorter retention time(p=0.0029).Conclusion:High-frequency stimulation in bilateral nucleus accumbens during abstinence period could attenuates relapse behavior in rats.Part Two: The Role of NMDA Receptors in Drug AddictionRelapse BehaviorObjective: To study the the role of NMDA receptors in drug addiction relapse behavior.Methods :Thirty adult SD rats,weighted 280g-300 g,electrode casing pipe was implanted into rats bilateral nucleus accumbens shell by stereotactic surgery,postoperative rest for 5d,Intraperitoneal injection of morphine(10mg/kg)induced rats to form conditioned position preference model.paired extinctive method was applied during extinguish process.rats were randomly divided into saline+DBS group、control group and AP-5+DBS group after successful extinction.Improving DBS system was used for electrical stimulation,the experimental group was given high frequency electrical stimulation(stimulation parameters: 120 HZ frequency,pulse width 60 ms,stimulation intensity of 0.3 m A,exciting time 30 min/d),control group set to false.AP-5 was microinjection into shell of AP-5+DBS group at the doze of 5ug on both sides 15 mins before stimulation,control group and saline+DBS group were replaced with saline,continuous stimulation for 7 days.Small doses of morphine to induce relapse within 24 h after last stimulation,then test CCP score and compared between groups.Result:1、After rats CPP paradigm establishment,rats spent 599.6s±63.27 s in the drug-paired chamber significantly longer than that before model establishment 379.4s±47.50s(p<0.0001),which indicated that the modeling was a success.2、The CPP score after extinction shows431.3s±130.9s,which show significant statistical difference compare to pre-conditioned CPP score 599.6s±63.27s(P<0.0001).Meanwhile have no significant statistical difference compare to postconditioned CPP score 379.4s±47.50s(P=0.2857),which indicated successful extinction.3、Comparison among groups:control group vs DBS group p<0.01,DBS group vs AP-5 group p<0.05.which show obvious difference.Conclusion:high-frequency stimulation in bilateral nucleus accumbens during abstinence period attenuates relapse behavior in rats can be reversed by microinjection with AP-5. |
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