Chronic methamphetamine self-administration dysregulates 5-HT2A and mGlu2 receptor expression in the rat prefrontal and perirhinal cortex: Comparison to chronic phencyclidine and MK-801.
Chronic methamphetamine self-administration dysregulates 5-HT2A and mGlu2 receptor expression in the rat prefrontal and perirhinal cortex: Comparison to chronic phencyclidine and MK-801.
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DOI：
10.1016/j.pbb.2018.09.007
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发表时间：
2018-12
期刊：
影响因子：
--
通讯作者：
Schwendt M
中科院分区：
文献类型：
--
作者：
Hámor PU;Šírová J;Páleníček T;Zaniewska M;Bubeníková-Valešová V;Schwendt M
慢性甲基苯丙胺(冰毒)滥用往往会转变为一种强迫性吸毒障碍，伴随着持续性的认知缺陷和复发的精神病。冰毒诱发的缺陷和精神分裂症可能的共同神经生物学底物仍然知之甚少。5-羟色胺2A(5-HT2A)和代谢性谷氨酸2(MGlu2)受体共同调节动物的精神病样行为和认知功能。因此，在本研究中，我们研究了慢性暴露于三种已知的导致感觉运动门控和认知障碍的不同药物[甲氧西林、苯环利定(PCP)和MK-801]对大鼠内侧前额叶皮质(PFC)、背海马(DHPC)和周围皮质(PRH)5-HT2A和mGlu2表达的影响。成年雄性大鼠连续14天给予冰毒(6小时/天)，(B)苯环利定(5 mg/kg，2次/d)，或(C)MK-801(0.3 mg/kg，2次/d)。停药7天后，收集感兴趣的组织进行蛋白质表达分析。我们发现，尽管有不同的药理作用机制，但慢性冰毒、五氯苯酚和MK-801对5-HT2A和mGlu2的调节相似，表现为mPFC(所有三种受试药物)、PRH(冰毒和五氯苯酚)和dHPC(仅MK-801)的5-HT2A/mGlu2表达比率增加。冰毒动物mPFC的G蛋白表达也出现了互补的变化(GαQ增加，GαI减少)。最后，我们发现5-HT2A/mGlu2的协同作用在一定程度上可以通过在某些皮质区域而不是所有皮质区域形成受体异构体来介导。综上所述，这些数据表明，皮质5-HT2a与mGlu2受体的可用性(和G蛋白偶联)增加，可能代表了在冰毒使用障碍和精神分裂症受试者中观察到的精神病和认知缺陷出现的常见神经生物学机制。
Chronic methamphetamine (meth) abuse often turns into a compulsive drug-taking disorder accompanied by persistent cognitive deficits and re-occurring psychosis. Possible common neurobiological substrates underlying meth-induced deficits and schizophrenia remain poorly understood. Serotonin 2A (5-HT2A) and metabotropic glutamate 2 (mGlu2) receptors coregulate psychosis-like behaviors and cognitive function in animals. Therefore, in the present study we examined the effects of chronic exposure to three different drugs known to produce persistent deficits in sensorimotor gating and cognition [meth, phencyclidine (PCP) and MK-801] on the expression of 5-HT2A and mGlu2 within the rat medial prefrontal cortex (PFC), dorsal hippocampus (dHPC) and perirhinal cortex (PRh). Adult male rats underwent 14 days of: (a) meth self-administration (6 hr/day), (b) phencyclidine (PCP; 5 mg/kg, twice/day) administration, or (c) MK-801 (0.3 mg/kg, twice/day) administration. Seven days after the discontinuation of drug administration, tissues of interest were collected for protein expression analysis. We found that despite different pharmacological mechanism of action, chronic meth, PCP, and MK-801 similarly dysregulated 5-HT2A and mGlu2, as indicated by an increase in the 5-HT2A/mGlu2 expression ratio in the mPFC (all three tested drugs), PRh (meth and PCP), and dHPC (MK-801 only). Complementary changes in G-protein expression (increase in Gαq and decrease in Gαi were also observed in the mPFC of meth animals. Finally, we found that 5-HT2A/mGlu2 cooperation can be mediated in part by the formation of the receptor heteromer in some, but not all cortical regions. In summary, these data suggest that a shift towards increased availability (and G-protein coupling) of cortical 5-HT2A vs. mGlu2 receptors may represent a common neurobiological mechanism underlying the emergence of psychosis and cognitive deficits observed in subjects with meth use disorder and schizophrenia.
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DOI：
10.1080/00207450802330702
发表时间：
2008-11
期刊：
The International journal of neuroscience
影响因子：
--
作者：
Ghose S;Crook JM;Bartus CL;Sherman TG;Herman MM;Hyde TM;Kleinman JE;Akil M
通讯作者：
Akil M
影响因子：
5.6
作者：
Corgiat BA;Nordman JC;Kabbani N
通讯作者：
Kabbani N
影响因子：
2.9
作者：
Brennan, Katharine A.;Colussi-Mas, Joyce;Schenk, Susan
通讯作者：
Schenk, Susan
影响因子：
5.3
作者：
Adams, B;Moghaddam, B
通讯作者：
Moghaddam, B
影响因子：
3.1
作者：
Choi, Yong Kee;Snigdha, Shikha;Tarazi, Frank I.
通讯作者：
Tarazi, Frank I.