von Euler G, Fuxe K, Hansson T, Ogren S O, Agnati L F, Eneroth P, Härfstrand A, Gustafsson J A
Department of Histology and Neurobiology, Karolinska Institute, Stockholm, Sweden.
Toxicology. 1988 Nov 14;52(1-2):103-26. doi: 10.1016/0300-483x(88)90199-0.
The effects of chronic toluene exposure (CTE) (80 ppm, 6 h/day, 5 days/week, 3 months) were studied on neuropeptide and 5-hydroxytryptamine receptors, on protein phosphorylation levels and on catecholamine levels in various brain regions in the 15-month-old male rat. Behavioral parameters and serum levels of hypophyseal hormones and corticosterone were also analyzed. CTE selectively reduced [3H]neurotensin [( 3H]NT) binding in the basal layers of the orbital cortex. Instead, CTE increased the binding of [3H]etorphine in the nucleus accumbens and of [125I]vasoactive intestinal polypeptide [( 125I]VIP) in the area postrema and hypoglossal nucleus. Acute treatment with the irreversible monoamine receptor antagonist N-ethoxycarboxyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) increased the binding of [3H]NT in the orbital cortex in toluene exposed rats as compared with the reduced [3H]NT binding obtained in air exposed rats treated with EEDQ. Furthermore, the EEDQ induced increase in [125I]VIP binding in the area postrema and the hypoglossal nucleus was replaced by a reduced binding of [125I]VIP in EEDQ-treated CTE rats. CTE produced an overall increase in calcium-induced back phosphorylation and an overall decrease in cyclic adenosine monophosphate-induced back phosphorylation in the frontoparietal cortex. Noradrenaline stores tended to be reduced within various hypothalamic subnuclei and the serum prolactin levels were increased following CTE. However, no marked effects of CTE were seen on the behavioral parameters. In conclusion, the regional selectivity of CTE in disturbing [3H]NT and [125I]VIP binding may be due to the demonstrated vulnerability of monoamine-neuropeptide interactions to toluene.
研究了慢性甲苯暴露（CTE）（80 ppm，每天6小时，每周5天，共3个月）对15月龄雄性大鼠不同脑区神经肽和5-羟色胺受体、蛋白质磷酸化水平以及儿茶酚胺水平的影响。还分析了行为参数以及垂体激素和皮质酮的血清水平。CTE选择性降低了眶皮质基底层中[3H]神经降压素[（3H]NT）的结合。相反，CTE增加了伏隔核中[3H]埃托啡的结合以及最后区和舌下神经核中[125I]血管活性肠肽[（125I]VIP）的结合。与暴露于空气并经不可逆单胺受体拮抗剂N-乙氧基羰基-2-乙氧基-1,2-二氢喹啉（EEDQ）处理的大鼠相比，用EEDQ对暴露于甲苯的大鼠进行急性处理增加了眶皮质中[3H]NT的结合。此外，EEDQ诱导的最后区和舌下神经核中[125I]VIP结合增加在EEDQ处理的CTE大鼠中被[125I]VIP结合减少所取代。CTE使额顶叶皮质中钙诱导的反向磷酸化总体增加，而环磷酸腺苷诱导的反向磷酸化总体减少。去甲肾上腺素储备在不同下丘脑亚核中趋于减少，CTE后血清催乳素水平升高。然而，未观察到CTE对行为参数有明显影响。总之，CTE在干扰[3H]NT和[125I]VIP结合方面的区域选择性可能是由于已证明的单胺 - 神经肽相互作用对甲苯的易损性。
