强迫性用药行为的神经生物学机制研究进展

Abstract

Compulsive drug use, or continual drug use despite punishment, is the core symptom of addiction. Drug addiction is associated with a shift from the response-outcome (R-O) process to the stimulus-response (S-R) process, such that it becomes habitual and ultimately compulsive. Previous studies have shown that this shift represents a transition at the neural level from ventral to more dorsal domains of the striatum, which is mediated by dopaminergic circuitry. However, a recent study indicated novel differentiation in dorsal striatum function. The midlateral striatum is involved in all stages of drug seeking after chronic self-administration training, whereas the dorsolateral striatum selectively participates in compulsive drug seeking. In addition, there is increasing evidence that chronic drug use can damage the prefrontal cortex. Indeed, different glutamatergic projections from the prefrontal cortex to the striatum play competing roles in drug seeking. These neural transitions depend on molecular mechanisms of neuroplasticity. An increasing number of studies have shown that low levels of D₂ receptors predict a switch to compulsive drug use. Additionally, recent studies indicated that 5-hydroxytryptamine also plays an important role in compulsive drug use.