Hanson G R, Singh N, Merchant K, Johnson M, Bush L, Gibb J W
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
Ann N Y Acad Sci. 1992;668:165-72. doi: 10.1111/j.1749-6632.1992.tb27348.x.
In summary, we have observed that drugs of abuse, which can cause schizophrenia-like paranoia, alter striatal and accumbens NT systems in a similar, dramatic fashion. The NT responses to these drugs, in particular METH, are mediated by activation of DA D1 receptors. We have observed that NMDA-type glutamate receptors are essential for the D1-NT interaction. NMDA receptors are selective, since they do not contribute to the antagonistic effects of DA D2 receptors on NT activity. This observation suggests that NT responses to D1 and D2 regulation are mediated through separate and distinct mechanisms. Finally, we found that the presence of METH dramatically reduces striatal NT release, which most likely leads to NT accumulation in nerve terminals and the observed increase in NT tissue level. The blockade of NT release by a psychotogenic drug, such as METH, is consistent with the hypothesis that NT has antipsychotic activity and a decrease in its release may contribute to some forms of schizophrenia similar to that caused by intense use of the stimulants of abuse.
总之，我们已经观察到，可导致精神分裂症样偏执狂的滥用药物，会以类似且显著的方式改变纹状体和伏隔核的神经递质系统。这些药物，尤其是甲基苯丙胺（METH），对神经递质的反应是由多巴胺D1受体的激活介导的。我们已经观察到，NMDA型谷氨酸受体对于D1-神经递质的相互作用至关重要。NMDA受体具有选择性，因为它们不会对多巴胺D2受体对神经递质活性的拮抗作用产生影响。这一观察结果表明，神经递质对D1和D2调节的反应是通过不同且独特的机制介导的。最后，我们发现甲基苯丙胺的存在会显著降低纹状体神经递质的释放，这很可能导致神经递质在神经末梢积累，进而观察到神经递质组织水平的升高。致幻药物（如甲基苯丙胺）对神经递质释放的阻断，与神经递质具有抗精神病活性的假设一致，其释放的减少可能导致某些形式的精神分裂症，类似于因大量使用滥用兴奋剂而导致的精神分裂症。
