Drug addiction is chronic recurring disease that results from prolonged effect of drugs on the brain. Early detection and prevention has been established that it is the best strategy for the drug addiction treatment. Mounting evidence showed that impulsivity can predict the severity of drug abuse, indicating impulsivity is a potential treatment target for early prevention. However, it is not clear what the development trajectories of impulsivity are as the drug dependence is spiraling upwards, and what is the alternation of impulsivity contributes to the emergence and persistence of compulsive drug seeking has not been investigated yet. In the present project, we aim to identify the relationship between the impulsivity trajectories and drug dependence combined clinic and preclinic studies. Firstly, the relationship between dynamic alternations of impulsivity and cue-induce drug craving war characterized in heroin, methamphetamine addicts and pathological gamblers after different length of drug abstinence duration, and the causal relationship between them was further examined in addicts in their initial phrase after receiving the cognitive behavioral training or transcranial magnetic stimulation intervention. Their frontostriatal neural correlates i are also to be investigated in addicts and gamblers who performing behavioral tasks to measure compulsive behavior or receiving drug-associated cues while undergoing functional magnetic resonance imaging. Lastly, rodent's model of drug addiction will be used to further explore the causal relationship between impulsivity alternations and drug dependence under strict control condition on drug exposure and abstinence duration. After characterizing the profile of compulsivity and drug seeking, the drug seeking motivation, compulsive behavior and cue-induced relapse are to examined in animals injected with different doses of anti-compulsivity drug atomoxetine when they are in their initial drug exposure or drug withdrawal periods. We apply for the in vivo calcium imaging to assess the dynamic effect by drug exposure on D1 OR D2 expressing neurons in striatum and prefrontal cortex in awaking animals. These studies will shed light on the causal relationship between the trajectories of impulsivity and emergence and persistence of compulsive drug seeking, and also provide helpful insights on early intervention of behavioral and drug addiction.
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