Study of neuroadaptive mechanisms for development of psychological dependence on volatile organic solvents.

甲苯和许多含有甲苯的产品被吸入滥用。为了评估甲苯吸入对小鼠的奖赏效应，建立了甲苯吸入的条件反射范式。吸入甲苯(700-3200ppm)在小鼠身上产生了显著的条件性位置偏爱。用多巴胺D1受体拮抗剂SCH23390预先处理甲苯，可消除甲苯的上述奖赏效应。甲苯吸入显著增加边缘前脑(伏隔核和嗅结节)的多巴胺水平。相比之下，吸入甲苯显著降低了边缘前脑中多巴胺代谢物(3，4-二羟基苯乙酸)的水平。这些结果表明，使用新开发的密封吸入盒的条件性位置偏爱程序为研究滥用溶剂的奖赏效应提供了一个重要的工具。此外，D1受体的激活可能在甲苯诱导的奖赏效应…的表达中起重要作用吸入甲苯可激活中脑边缘多巴胺系统的功能。中脑边缘多巴胺系统的改变可能参与甲苯诱导的小鼠奖赏效应的表达。此外，还研究了甲苯吸入对脑内c-Fos蛋白表达的影响，以确定甲苯吸入最敏感的解剖底物。此外，还观察了cAMP水平和cAMP反应元件结合蛋白(CREB)蛋白表达的影响。甲苯吸入后，c-Fos蛋白在边缘前脑和海马区的表达选择性增加，提示这些脑区可能是甲苯吸入的解剖学基础。此外，反复吸入甲苯增加了边缘前脑中cAMP和磷酸化CREB蛋白的水平。这些结果提示，反复吸入甲苯后腺酰环化酶系统的适应可能在甲苯奖赏效应的形成中起重要作用。较少

Toluene and many toluene-containing products are abused via inhalation. A conditioning paradigm of toluene inhalation was developed in order to estimate the rewarding effect in mice. Toluene inhalation (700-3200ppm) produced a significant conditioned place preference in mice. These rewarding effects of toluene were abolished by pretreatment with dopamine D1 receptor antagonist SCH23390. Toluene inhalation significantly increased the dopamine level in the limbic forebrain (nucleus accumbens and olfactory tubercle). In contrast, toluene inhalation significantly decreased the dopamine metabolite (3,4-dihydroxyphenylacetic acid) level in the limbic forebrain. These results suggest that the conditioned place preference procedure using a newly developed novel sealed inhalation shuttlebox offers an important tool for studying the rewarding effect of abused solvents. Furthermore, the activation of D1 receptors may play an important role in the expression of the toluene-induced rewarding effect … More s. Toluene inhalation could activate the function of the mesolimbic dopamine system. Modification of the mesolimbic dopamine system may be involved in the expression of toluene-induced rewarding effect in mice. Furthermore, the effect of toluene inhalation on c-Fos protein expression in the brain to identify the most sensitive anatomical substrates for toluene inhalation was investigated. The influences of the cyclic AMP level and the cyclic AMP response element binding (CREB) protein expression were also examined. After toluene inhalation, the expression of c-Fos protein was found to have selectively increased in the limbic forebrain and the hippocampus, indicating that these brain regions may be anatomical substrates for toluene inhalation. Furthermore, repeated toluene inhalation increased the levels of cAMP and phospho-CREBproteins in the limbic forebrain. These results suggest that adaptation of the adenylyl cyclase system after repeated toluene inhalation may play an important role in the development of the rewarding effect of toluene. Less