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首页> 外文期刊>Brain research >Role of NMDA receptor subtypes in the induction of catalepsy and increase in Fos protein expression after administration of haloperidol.
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Role of NMDA receptor subtypes in the induction of catalepsy and increase in Fos protein expression after administration of haloperidol.

机译：氟哌啶醇给药后，NMDA受体亚型在诱导僵直症和增加Fos蛋白表达中的作用。

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The increase of Fos expression in the striatum induced by haloperidol, an antagonist of the dopamine D(2) receptor, might be related to the activation of glutamatergic neurotransmission, especially that of N-methyl-d-aspartate (NMDA) receptors. In this study, using behavioral and immunohistochemical techniques, we examined the effects of a noncompetitive NMDA antagonist, (+)-MK-801, and an NMDA receptor NR2B subunit antagonist, ifenprodil, on catalepsy, an extrapyramidal symptom; in this context, we also considered the expression of Fos protein in the forebrain after the administration of haloperidol. Catalepsy in mice, induced by the administration of haloperidol (1 mg/kg), was inhibited by pretreatment with (+)-MK-801 (0.2 mg/kg) or ifenprodil (10 mg/kg). Furthermore, pretreatment with (+)-MK-801 (0.2 mg/kg) significantly attenuated the induction of Fos-immunoreactive (IR) cells in the dorsomedial, dorsolateral, and ventrolateral striatum, but not in the shell region of the nucleus accumbens after the administration of haloperidol, whereas pretreatment with ifenprodil (10 mg/kg) significantly attenuated the induction of Fos-IR cells in all of these areas. It is known that ifenprodil binds sigma receptors and alpha-1 adrenergic receptors with high affinity. Pretreatment with the sigma receptor antagonist BD-1407 (3 mg/kg) or the alpha-1 adrenergic receptor antagonist prazosin (3 mg/kg) affected neither catalepsy nor the expression of Fos-IR cells after the administration of haloperidol. However, pretreatment with CP-101,606 (1 mg/kg), a selective antagonist for the NR2B subunit of the NMDA receptor, significantly attenuated catalepsy and the expression of Fos-IR cells in the forebrain after the administration of haloperidol. These results suggest that the NMDA receptor antagonists attenuated the induction of catalepsy and Fos-IR cells in forebrain after the administration of haloperidol. It was also suggested that haloperidol-induced expression of Fos-IR cells in the shell region of the nucleus accumbens might be differentially regulated by NMDA receptor subunits. Therefore, it appears that selective antagonists for the NR2B subunit of the NMDA receptor (e.g., CP-101,606) might be useful drugs for the treatment of extrapyramidal side effects (EPS) associated with the chronic use of typical antipsychotics such as haloperidol.
机译：氟哌啶醇（一种多巴胺D（2）受体的拮抗剂）诱导的纹状体中Fos表达的增加可能与谷氨酸能神经传递，尤其是N-甲基-d-天冬氨酸（NMDA）受体的激活有关。在这项研究中，我们使用行为和免疫组化技术，研究了非竞争性NMDA拮抗剂（+）-MK-801和NMDA受体NR2B亚基拮抗剂ifenprodil对僵直症（锥体外系症状）的影响;在这种情况下，我们还考虑了氟哌啶醇给药后前脑中Fos蛋白的表达。给予氟哌啶醇（1 mg / kg）引起的小鼠僵直症通过（+）-MK-801（0.2 mg / kg）或艾芬洛地尔（10 mg / kg）的预处理得到抑制。此外，用（+）-MK-801（0.2 mg / kg）进行的预处理可显着减弱背部，背部和腹侧纹状体中Fos免疫反应（IR）细胞的诱导，但是在之后的伏隔核壳区域中却没有氟哌啶醇的给药，而用艾芬地尔（10 mg / kg）预处理则显着减弱了所有这些区域中Fos-IR细胞的诱导。已知艾芬洛地尔以高亲和力结合σ受体和α-1肾上腺素能受体。给予氟哌啶醇后，使用sigma受体拮抗剂BD-1407（3 mg / kg）或α-1肾上腺素能受体拮抗剂prazosin（3 mg / kg）进行预处理既不会影响僵直症也不会影响Fos-IR细胞的表达。然而，使用氟哌啶醇后，用CP-101,606（1 mg / kg）（一种NMDA受体NR2B亚基的选择性拮抗剂）进行预处理可显着减弱前臂僵直症和前脑Fos-IR细胞的表达。这些结果表明，在给予氟哌啶醇后，NMDA受体拮抗剂减弱了前脑中僵直症和Fos-IR细胞的诱导作用。还提出了氟哌啶醇诱导的伏伏核细胞壳区域中Fos-IR细胞的表达可能受到NMDA受体亚单位的差异调节。因此，看来NMDA受体的NR2B亚单位的选择性拮抗剂（例如CP-101,606）可能是用于治疗与长期使用典型抗精神病药如氟哌啶醇有关的锥体束外副作用（EPS）的有用药物。

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