| Background and aim:Drug addiction is a huge disaster to addicts, their families and the society. Although many therapies could help addicts fight physical dependence and reach detoxification safely, they couldn't suppress drug craving much. Most patients relapse after successful detoxification. Some researchers try to treat relapse with stereotactic operation. They hypothesized drug craving can be restrained by lesions of specific brain areas. Pilot clinical trials and preclinical studies hint nucleus accumbens (NAc) is an effective target to prevent relapse. Since past operation made permanent lesions to the brain, it brought great ethical controversy. Deep brain stimulation (DBS) developed and has been replacing lesions progressively, which is non-invasive and reversible. Therefore, we explored DBS treatment to drug addiction in this research. Cocaine self-administration was established in rhesus monkeys whose NAc were inserted with electrodes. Electrical stimulation was delivered through the electrodes and its effect on cocaine reinforcement and craving was investigated.Method: (1) An adaptor was designed and made, which can fasten the monkey skull and connect to stereotactic hand ring firmly. In this way the targets in the monkey brain could be located by MRI-guided stereotactic technique which is used for human. With the help of adaptor and clinical stereotactic technique, electrodes were implanted in bilateral nucleus accumbens in 4 rhesus monkeys. The positions of electrodes were verified by MRI scan at 1 week after operation.(2) The 4 rhesus monkeys were trained to cocaine self-administration at 0.1 mg per kilogram of body weight in one injection. Fixed-ratio (FR) was employed at first, and the ratio was increased from 1 to 10. When FR10 self-administration was stable, the response rates were recorded. Then electrical stimulation under three different parameters was given to animals successively, and the changes of response rate were investigated.(3) Progressive-ratio (PR) cocaine self-administration were carried out later and the breaking points were acquired. Electrical stimulation was delivered to NAc and the parameter was set to 1.8V, 130Hz, 90μs. The changes of breaking point were investigated.Result:(1)MRI scan showed the distance between position of electrodes and scheduled targets were 0.64±0.28mm in anterior-posterior direction, and 0.34±0.17mm in left-right direction.(2)The response/session in FR10 cocaine self-administration was 382.5±45.02. When electrical stimulation under three different parameters were given, the responses/session were 364.75±52.29,359±63.44 and 253.25±25.62. The response/session was decreased significantly when the parameter was set to 1.8V, 130Hz, 90μs (P<0.05).(3)The breaking point under PR cocaine self-administration was 61.08±9.24. It decreased to 31.25±9.61 when the electrical stimulation (1.8V, 130Hz, 90μs) was given to NAc(P<0.01).Conclusion:(1)With the adaptor, nucleus and region in monkey brain could be located individually under MRI scan. The electrodes were implanted in NAc accurately.(2)Bilateral NAc stimulation could decrease response/session in FR10 cocaine self-administration and breaking point in PR cocaine self-administration, when the parameter of stimulation was 1.8V, 130Hz, 90μs. It demonstrated NAc stimulation can suppress cocaine reinforcement and craving. |
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