Yoshida Y, Ono T, Kawano K, Miyagishi T
Department of Psychiatry and Neurology, Asahikawa Medical College, Hokkaido, Japan.
Brain Res. 1994 Mar 7;639(1):139-48. doi: 10.1016/0006-8993(94)91774-4.
Previous studies have indicated that corticostriatal glutamatergic pathways are implicated in the regulation of neuroleptic catalepsy. To obtain a better understanding of the way in which dopamine (DA) and glutamate interact within the caudate-putamen (CP) in the development of catalepsy, we investigated the regional distribution within the rat CP of the cataleptogenic effect of haloperidol and its antagonism by D(-)-2-amino-5-phosphonopentanoic acid (D(-)AP5), a selective antagonist of the N-methyl-D-aspartate (NMDA) glutamate receptor subtype. Bilateral injections of haloperidol (3 micrograms/side) into the rostral ventromedial (VM) CP induced potent catalepsy with a short latency after the injection. In contrast, only a weak cataleptic response, of slower onset, was observed after haloperidol injections into the rostral ventrolateral (VL), rostral dorsomedial (DM), or rostral dorsolateral (DL) CP, or into the nucleus accumbens. D(-)AP5 (5 micrograms/side) injected bilaterally into the dorsorostral CP (DM and DL) strongly inhibited the catalepsy induced by systemic haloperidol (1 mg/kg, i.p.), and this effect lasted longer when the drug was injected into the DM than when it was injected into the DL. D(-)AP5 did not affect haloperidol-induced catalepsy when injected into the ventrorostral (VM and VL) or intermediate dorsal CP. D(-)AP5 injected into the DM, the region most sensitive to the anticataleptic effect of the drug, had no effect on basal levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, or on the modification of these levels by haloperidol in either the DM or VM. These findings suggest that, while the catalepsy resulting from DA receptor blockade by haloperidol originates mainly from the VM, the expression of this phenomenon depends on an intact glutamatergic transmission within the dorsorostral CP. In the development of neuroleptic catalepsy, the mesencephalostriatal DAergic and corticostriatal glutamatergic pathways seem to be functionally linked through an indirect, rather than a direct, interaction.
以往的研究表明，皮质纹状体谷氨酸能通路与抗精神病药物所致僵住症的调节有关。为了更好地理解在僵住症发生过程中多巴胺（DA）和谷氨酸在尾状核 - 壳核（CP）内的相互作用方式，我们研究了氟哌啶醇致僵住效应在大鼠CP内的区域分布，以及D -（-）-2 - 氨基 - 5 - 膦酰基戊酸（D -（-）AP5，一种N - 甲基 - D - 天冬氨酸（NMDA）谷氨酸受体亚型的选择性拮抗剂）对其的拮抗作用。向尾状核头腹内侧（VM）双侧注射氟哌啶醇（3微克/侧）后，注射后潜伏期短，可诱导出强烈的僵住症。相比之下，向尾状核头腹外侧（VL）、头背内侧（DM）或头背外侧（DL）CP或伏隔核注射氟哌啶醇后，仅观察到较弱的僵住反应，且起效较慢。双侧向背侧头端CP（DM和DL）注射D -（-）AP5（5微克/侧）可强烈抑制全身注射氟哌啶醇（1毫克/千克，腹腔注射）诱导的僵住症，且该药物注射到DM时这种作用持续时间比注射到DL时更长。当注射到腹侧头端（VM和VL）或中间背侧CP时，D -（-）AP5不影响氟哌啶醇诱导的僵住症。注射到对该药物抗僵住效应最敏感的区域DM的D -（-）AP5，对DA及其代谢产物3,4 - 二羟基苯乙酸和高香草酸的基础水平，或对DM或VM中氟哌啶醇对这些水平的改变均无影响。这些发现表明，虽然氟哌啶醇阻断DA受体所致的僵住症主要源于VM，但这种现象的表达取决于背侧头端CP内完整的谷氨酸能传递。在抗精神病药物所致僵住症的发生过程中，中脑纹状体DA能和皮质纹状体谷氨酸能通路似乎通过间接而非直接的相互作用在功能上相联系。
