Department of Psychology, Wayne State University, Detroit, MI, United States; The Behavioral Neuroscience of Social Relationships Laboratory, Wayne State University, Detroit, MI, United States.
Neurotoxicol Teratol. 2013 Nov-Dec;40:28-34. doi: 10.1016/j.ntt.2013.09.001. Epub 2013 Sep 12.
Toluene is a frequently abused solvent. Previous studies have suggested that toluene acts like other drugs of abuse, specifically on the dopaminergic system in the nucleus accumbens (NAc) and ventral tegmental area (VTA) of the mesolimbic pathway. Although changes in dopamine (DA) levels and c-Fos have been observed in both acute and repeated exposure paradigms, the extent to which c-Fos is localized to catecholaminergic cells is unknown. The present study tested the effects of repeated toluene exposure (1000-4000ppm) on locomotor activity and cells containing c-Fos, tyrosine hydroxylase (TH), or both in the core and shell of the NAc, as well as the anterior and posterior VTA. We focused our study on adolescents, since adolescence is a time of great neural change and a time when individuals tend to be more susceptible to drug abuse. In early tests, toluene dose-dependently increased locomotor activity. Repeated exposure to the highest concentration of toluene resulted in sensitization to toluene's effects on locomotor activity. Although the number of cells immunopositive for c-Fos or TH did not significantly differ across groups, cells immunopositive for TH+c-Fos were higher in the NAc shell of animals exposed to 4000ppm than in animals exposed to air (control) or 1000ppm. Taken together, these findings demonstrate that repeated high dose toluene exposure increases locomotor activity as well as activation of catecholaminergic cells in the shell of the NAc.
甲苯是一种经常被滥用的溶剂。以前的研究表明，甲苯的作用类似于其他滥用药物，特别是在伏隔核（NAc）和中脑边缘多巴胺系统的腹侧被盖区（VTA）。尽管在急性和重复暴露范式中都观察到了多巴胺（DA）水平和 c-Fos 的变化，但 c-Fos 在儿茶酚胺能细胞中的定位程度尚不清楚。本研究测试了重复暴露于甲苯（1000-4000ppm）对运动活动以及 NAc 核和壳中的含有 c-Fos、酪氨酸羟化酶（TH）或两者的细胞的影响，以及 VTA 的前侧和后侧。我们的研究集中在青少年身上，因为青少年时期是神经变化的重要时期，也是个体更容易滥用药物的时期。在早期测试中，甲苯呈剂量依赖性地增加运动活动。重复暴露于最高浓度的甲苯会导致对甲苯对运动活动的影响产生敏化作用。尽管免疫阳性的 c-Fos 或 TH 细胞的数量在各组之间没有显著差异，但暴露于 4000ppm 甲苯的动物的 NAc 壳中免疫阳性的 TH+c-Fos 细胞高于暴露于空气（对照）或 1000ppm 的动物。综上所述，这些发现表明，重复高剂量甲苯暴露会增加运动活动以及 NAc 壳中儿茶酚胺能细胞的激活。
