von Euler G, Ogren S O, Bondy S C, McKee M, Warner M, Gustafsson J A, Eneroth P, Fuxe K
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Toxicology. 1991 May;67(3):333-49. doi: 10.1016/0300-483x(91)90032-v.
The effects of low concentrations of toluene (40-80 ppm, 3 days, 6 h/day) were investigated on spontaneous and on apomorphine-induced locomotor activity in the rat, and were correlated to effects on S(-)[N-propyl-3H(N)]-propylnorapomorphine ([3H]NPA) binding in rat neostriatal membranes, on membrane fluidity, membrane leakage, and calcium levels in synaptosomes from the frontoparietal cortex, the neostriatum and the subcortical limbic area, and on serum hormone levels. Toluene exposure (80 ppm, post-exposure delay 18 h) alone did not affect locomotor activity, but attenuated apomorphine-induced (0.05 mg/kg, s.c.) suppression of rearing, and potentiated apomorphine-induced (1 mg/kg, s.c.) increases in locomotion and rearing. Toluene exposure increased the KD value of [3H]NPA binding without affecting the Bmax. All these effects were absent at 40 ppm of toluene or at a post-exposure delay of 42 h. Toluene exposure (80 ppm, post-exposure delay of 18 h) did not affect the serum levels of prolactin, TSH, corticosterone, or aldosterone, or synaptosomal membrane fluidity and calcium levels, whereas membrane leakage was increased in the neostriatum. The present study indicates that the reduction of D-2 receptor affinity by short-term, low-dose toluene exposure is accompanied by a reduced D-2 autoreceptor function and an enhanced postsynaptic D-2 receptor function.
研究了低浓度甲苯(40 - 80 ppm,3天,每天6小时)对大鼠自发运动和阿扑吗啡诱导的运动活动的影响,并将其与对大鼠新纹状体膜中S(-)[N-丙基-3H(N)]-丙基去甲阿扑吗啡([3H]NPA)结合、膜流动性、膜通透性以及额叶顶叶皮质、新纹状体和皮质下边缘区域突触体中钙水平的影响,以及对血清激素水平的影响进行关联分析。单独暴露于甲苯(80 ppm,暴露后延迟18小时)不影响运动活动,但减弱了阿扑吗啡诱导的(0.05 mg/kg,皮下注射)竖毛抑制作用,并增强了阿扑吗啡诱导的(1 mg/kg,皮下注射)运动和竖毛增加作用。甲苯暴露增加了[3H]NPA结合的KD值,而不影响Bmax。在40 ppm甲苯或暴露后延迟42小时时,所有这些影响均不存在。甲苯暴露(80 ppm,暴露后延迟18小时)不影响催乳素、促甲状腺激素、皮质酮或醛固酮的血清水平,也不影响突触体膜流动性和钙水平,而新纹状体中的膜通透性增加。本研究表明,短期、低剂量甲苯暴露导致D-2受体亲和力降低的同时,伴随着D-2自身受体功能降低和突触后D-2受体功能增强。