Schizophrenia is associated with three main categories of symptoms; positive, negative and cognitive. Of these, only the positive symptoms respond well to treatment with antipsychotics. Due to the lack of effect of antipsychotics on negative symptoms, it has been suggested that while the positive symptoms are related to a hyperdopaminergic state in associative striatum, the negative symptoms may be a result of a reduced dopamine (DA) activity in the nucleus accumbens (nAc). Drug abuse is common in schizophrenia, supposedly alleviating negative symptomatology. Some, but not all, drugs aggravate psychosis, tentatively due to differential effects on DA activity in striatal regions. Here this hypothesis was tested in rats by using a double-probe microdialysis technique to simultaneously assess DA release in the nAc and associative striatum (dorsomedial striatum; DMS) following administration of the psychosis-generating substances amphetamine (0.5 mg/kg), cocaine (15 mg/kg) and Δ⁹-tetrahydrocannabinol (THC, 3 mg/kg), and the generally non-psychosis-generating substances ethanol (2.5 g/kg), nicotine (0.36 mg/kg) and morphine (5 mg/kg). The data show that amphetamine and cocaine produce identical DA elevations both in the nAc and DMS, whereas nicotine increases DA in nAc only. Ethanol and morphine both increased DMS DA, but weaker and in a qualitatively different way than in nAc, suggesting that the manner in which DA is increased might be important to the triggering of psychosis. THC elevated DA in neither region, indicating that the pro-psychotic effects of THC are not related to DA release. We conclude that psychosis-generating substances affect striatal DA release differently than non-psychosis-generating substances.

精神分裂症与三大类症状有关；积极的，消极的和认知的。其中，只有阳性症状对抗精神病药物治疗反应良好。由于抗精神病药对阴性症状缺乏影响，有人提出虽然阳性症状与联想纹状体中的高多巴胺能状态有关，但阴性症状可能是伏隔核中多巴胺 (DA) 活性降低的结果(nAc)。药物滥用在精神分裂症中很常见，据称可以减轻阴性症状。一些（但不是全部）药物会加重精神病，暂时是由于对纹状体区域 DA 活动的不同影响。^9-四氢大麻酚（THC，3 毫克/千克），以及一般不会产生精神病的物质乙醇（2.5 克/千克）、尼古丁（0.36 毫克/千克）和吗啡（5 毫克/千克）。数据显示苯丙胺和可卡因在 nAc 和 DMS 中产生相同的 DA 升高，而尼古丁仅增加 nAc 中的 DA。乙醇和吗啡都增加了 DMS DA，但比 nAc 更弱且质量不同，这表明增加 DA 的方式可能对引发精神病很重要。THC 两个区域的 DA 均升高，表明 THC 的促精神病作用与 DA 释放无关。我们得出结论，精神病产生物质对纹状体 DA 释放的影响不同于非精神病产生物质。