Ahn Sung Min, Kim Soo Woon, Choe Eun Sang
Division of Biological Sciences, Pusan National University, 30 Jangjeon-dong, Kumjeong-gu, Pusan, 609-735, South Korea.
Psychopharmacology (Berl). 2007 Dec;195(3):407-14. doi: 10.1007/s00213-007-0922-9. Epub 2007 Sep 13.
Cocaine increases endoplasmic reticulum (ER) stress protein expression via glutamate and dopamine receptor activation in the dorsal striatum.
The present study was performed to investigate ER stress response in the dorsal striatum in response to acute or repeated cocaine stimulation. It was hypothesized that cocaine upregulates the ER stress protein immunoglobulin heavy chain binding protein (BiP) and the ER stress-associated protein caspase-12 via N-methyl-D-aspartate (NMDA) and D1 dopamine receptor activation.
Western immunoblot and immunohistochemical analyses were mainly performed to test this hypothesis in the rat dorsal striatum.
The results showed that BiP and caspase-12 immunoreactivities were significantly increased at 30, 60, and 120 min after acute or repeated intraperitoneal (i.p.) injections of three doses (10, 20, 40 mg/kg) of cocaine for seven consecutive days. Intrastriatal (i.s.) infusion of the selective NMDA antagonist MK801 (2 nmol) or AP5 (2 nmol) significantly attenuated the increase in the immunoreactivity of caspase-12 in the dorsal striatum induced by repeated, but not acute, cocaine (20 mg/kg) administration. However, i.p. injection of the selective D1 antagonist SCH23390 (0.1 mg/kg) significantly attenuated the increase in the immunoreactivity of caspase-12 in the dorsal striatum induced by both acute and repeated cocaine (20 mg/kg) stimulation.
These findings suggest that acute or repeated cocaine administration can cause ER stress response in the dorsal striatum in which NMDA and D1 dopamine receptors participate in the mediation of the process.
可卡因通过激活背侧纹状体中的谷氨酸和多巴胺受体来增加内质网（ER）应激蛋白的表达。
本研究旨在探究背侧纹状体在急性或反复可卡因刺激下的内质网应激反应。研究假设可卡因通过N-甲基-D-天冬氨酸（NMDA）和D1多巴胺受体激活，上调内质网应激蛋白免疫球蛋白重链结合蛋白（BiP）和内质网应激相关蛋白半胱天冬酶-12。
主要通过蛋白质免疫印迹和免疫组织化学分析在大鼠背侧纹状体中验证这一假设。
结果显示，连续七天腹腔注射三剂（10、20、40mg/kg）可卡因后，在30、60和120分钟时，急性或反复注射组的BiP和半胱天冬酶-12免疫反应性显著增加。纹状体内注射选择性NMDA拮抗剂MK801（2nmol）或AP5（2nmol）可显著减弱反复（而非急性）注射可卡因（20mg/kg）诱导的背侧纹状体中半胱天冬酶-12免疫反应性的增加。然而，腹腔注射选择性D1拮抗剂SCH23390（0.1mg/kg）可显著减弱急性和反复注射可卡因（20mg/kg）刺激诱导的背侧纹状体中半胱天冬酶-12免疫反应性的增加。
这些发现表明，急性或反复给予可卡因可导致背侧纹状体发生内质网应激反应，其中NMDA和D1多巴胺受体参与了该过程的介导。
