Plasticity of reward neurocircuitry and the 'dark side' of drug addiction.

摘要: Drug seeking is associated with activation of reward neural circuitry. Here we argue that drug addiction also involves a ‘dark side’—a decrease in the function normal reward-related neurocircuitry and persistent recruitment anti-reward systems. Understanding neuroplasticity dark side this circuitry key to understanding vulnerability addiction. has been conceptualized as progression from impulsive compulsive behavior, ending chronic, relapsing taking. Patients impulse control disorders experience an increasing sense tension or arousal before committing act; pleasure, gratification relief at time then regret, selfreproach guilt after act 1 . In contrast, patients anxiety stress repetitive by performing behavior addiction, drug-taking progresses impulsivity compulsivity three-stage cycle: binge/intoxication, withdrawal/negative affect preoccupation/anticipation 2 stage, drive for positive reinforcement, which stimuli increase probability response. As individuals move transitions negative removal aversive state increases Different theoretical perspectives experimental psychology (positive reinforcement framework), social (self-regulation failure framework) neurobiology (counteradaptive sensitization can be superimposed on stages cycle These are thought feed into each other, becoming more intense ultimately leading pathological known Our thesis longterm, plasticity activity circuits mediating two different motivational systems: decreased brain systems driven natural rewards, states. The concept based hypothesis there place limit (see footnote ref. 2), ‘opponent process’ general feature biological 3 From neurobiological perspective, through three induces drives taking, narrowing behavioral repertoire seeking. Animal models have developed face validity (resembles human condition) some construct (possesses explanatory power) all transition Acute selfadministration drugs (intravenous oral) intoxication elements binges humans. Self-stimulation conditioning (learning avoid location previously paired stimulus state) sensitive measures ‘motivational’ withdrawal. Cue-induced