Zavala Arturo R, Browning Jenny R, Dickey Erin D, Biswas Sudipta, Neisewander Janet L
Department of Psychology, Arizona State University, Box 871104, Tempe, AZ 85287-1104, United States.
Eur Neuropsychopharmacol. 2008 Aug;18(8):600-11. doi: 10.1016/j.euroneuro.2008.04.010. Epub 2008 Jun 6.
This study investigated the effects of the AMPA/Kainate receptor antagonist, NBQX, on cue-elicited cocaine-seeking behavior and concomitant changes in Fos protein expression. After cocaine self-administration training, rats underwent 24 days of abstinence during which they were exposed daily either to the self-administration environment with response-contingent cues previously paired with cocaine infusions available (Extinction group) or to an alternate environment (No Extinction group). Subsequently, rats were tested for cocaine-seeking behavior (i.e., operant responses without cocaine reinforcement) elicited by the cocaine-associated cues after pretreatment with either vehicle or NBQX (10 mg/kg, IP). NBQX markedly attenuated cue-elicited cocaine-seeking behavior relative to vehicle pretreatment in the No Extinction group and also decreased cue-elicited Fos protein expression in a region-specific manner in the anterior cingulate and orbitofrontal cortices, basolateral amygdala, nucleus accumbens core, and dorsal caudate-putamen, suggesting involvement of AMPA glutamate systems in specific subregions of the neuronal circuitry activated by cocaine cues.
本研究调查了AMPA/海人酸受体拮抗剂NBQX对线索诱发的可卡因觅求行为以及Fos蛋白表达伴随变化的影响。在可卡因自我给药训练后,大鼠经历24天的戒断期,在此期间,它们每天要么暴露于与之前可卡因输注配对的有反应条件线索的自我给药环境中(消退组),要么暴露于另一个环境中(无消退组)。随后,在用溶剂或NBQX(10mg/kg,腹腔注射)预处理后,测试大鼠对可卡因相关线索诱发的可卡因觅求行为(即无可卡因强化的操作性反应)。与无消退组中溶剂预处理相比,NBQX显著减弱了线索诱发的可卡因觅求行为,并且还以区域特异性方式降低了前扣带回和眶额皮质、基底外侧杏仁核、伏隔核核心以及背侧尾状核-壳核中线索诱发的Fos蛋白表达,提示AMPA谷氨酸系统参与了由可卡因线索激活的神经回路特定亚区域。