PDF(Pubmed)
Abstract：
Glutamate receptors have a key role in the neurobiology of opioid addiction. Using electron microscopic immunocytochemical methods, this project elucidates how sex and chronic immobilization stress (CIS) impact the redistribution of GluN1 and GluA1 within rat hippocampal CA3 pyramidal cells following oxycodone (Oxy) conditioned place preference (CPP). Four groups of female and male Sprague-Dawley rats subjected to CPP were used: Saline- (Sal) and Oxy-injected (3 mg/kg, I.P.) naïve rats; and Sal- and Oxy-injected CIS rats. GluN1: In both naive and CIS rats, Sal-females compared to Sal-males had elevated cytoplasmic and total dendritic GluN1. Following Oxy CPP, near plasmalemmal, cytoplasmic, and total GluN1 decreased in CA3 dendrites of unstressed females suggesting reduced pools of GluN1 available for ligand binding. Following CIS, Oxy-males (which did not acquire CPP) had increased GluN1 in all compartments of dendrites and spines of CA3 neurons. GluA1: There were no differences in the distribution GluA1 in any cellular compartments of CA3 dendrites in naïve females and males following either Sal or Oxy CPP. CIS alone increased the percent of GluA1 in CA3 dendritic spines in males compared to females. CIS Oxy-males compared to CIS Sal-males had an increase in cytoplasmic and total dendritic GluA1. Thus, in CIS Oxy-males increased pools of GluN1 and GluA1 are available for ligand binding in CA3 neurons. Together with our prior experiments, these changes in GluN1 and GluA1 following CIS in males may contribute to an increased sensitivity of CA3 neurons to glutamate excitation and a reduced capacity to acquire Oxy CPP.
摘要：
谷氨酸受体在阿片成瘾的神经生物学中起关键作用。使用电子显微镜免疫细胞化学方法，该项目阐明了性和慢性固定应激（CIS）如何影响羟考酮（Oxy）条件位置偏爱（CPP）后大鼠海马CA3锥体细胞中GluN1和GluA1的再分布。使用四组接受CPP的雌性和雄性Sprague-Dawley大鼠：注射盐水（Sal）和Oxy（3mg/kg，I.P.)幼稚大鼠；以及盐和氧注射CIS大鼠。GluN1：在幼稚和CIS大鼠中，与Sal雄性相比，Sal雌性的细胞质和总树突GluN1升高。遵循OxyCPP，在浆膜附近，细胞质，无应力雌性的CA3树突中的总GluN1减少，表明可用于配体结合的GluN1池减少。遵循CIS，Oxy雄性（未获得CPP）在CA3神经元的树突和棘的所有区室中都增加了GluN1。GluA1:在Sal或OxyCPP之后的初始雌性和雄性中,在CA3树突的任何细胞区室中GluA1的分布没有差异。与女性相比，CIS单独增加了男性CA3树突棘中GluA1的百分比。CISOxy男性与CISSal男性相比，细胞质和总树突GluA1增加。因此，在CISOxy-雄性增加的GluN1和GluA1库可用于CA3神经元中的配体结合。再加上我们之前的实验,男性CIS后GluN1和GluA1的这些变化可能导致CA3神经元对谷氨酸兴奋的敏感性增加和获得OxyCPP的能力降低。
