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

甲苯和许多含甲苯的产品通过吸入被滥用。建立了甲苯吸入条件反射模型，以评价甲苯吸入对小鼠的奖赏效应。吸入甲苯（700- 3200 ppm）可使小鼠产生明显的条件性位置偏爱。预先用多巴胺D1受体拮抗剂SCH 23390处理，甲苯的这些奖赏效应被消除。甲苯吸入显著增加边缘前脑（丘脑核和嗅结节）的多巴胺水平。相比之下，甲苯吸入显着降低多巴胺代谢产物（3，4-二羟基苯乙酸）在边缘前脑的水平。这些结果表明，条件性位置偏爱程序使用一种新开发的新型密封吸入梭箱提供了一个重要的工具，用于研究滥用溶剂的奖励效应。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 关于我们 S.甲苯吸入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了甲苯诱导的奖赏效应的表达。此外，甲苯吸入对脑中c-Fos蛋白表达的影响进行了研究，以确定甲苯吸入最敏感的解剖学底物。环磷酸腺苷水平和环磷酸腺苷反应元件结合（CREB）蛋白表达的影响也进行了检查。甲苯吸入后，c-Fos蛋白的表达被发现有选择性地增加，在边缘前脑和海马，表明这些脑区可能是甲苯吸入的解剖基质。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。这些结果表明，适应腺苷酸环化酶系统反复吸入甲苯后，可能发挥了重要的作用，甲苯的奖励效应的发展。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