Rebert C S, Matteucci M J, Pryor G T
SRI International, Menlo Park, CA 94025.
Pharmacol Biochem Behav. 1989 Mar;32(3):757-68. doi: 10.1016/0091-3057(89)90030-0.
Male Fischer-344 rats were exposed by inhalation to 500, 2000, 5000, 8000 and 16000 ppm toluene for 30 min in two experiments. Exposures up to 8000 ppm in Experiment 1 caused concentration-related changes in the click-elicited brainstem auditory-evoked response (CBAER), flash-evoked potential (FEP) and somatosensory-evoked potential (SEP). Latencies of CBAER components were prolonged and amplitudes of late components were increased by toluene. Toluene did not detectably alter the latencies of FEP or SEP components. Early FEP component-amplitudes were increased and late component-amplitudes were decreased; toluene also induced a poststimulus oscillation in the FEP. Most component-amplitudes of the SEP were substantially increased, but N2P2 amplitude appeared to be more sensitive than other components to depressant effects of the solvent. The same effects on the CBAER were observed in Experiment 2, but a more substantial increase in the amplitudes of late components elicited by tone pips suggested that frequency-dependent cochlear irritation might underlie previously observed subchronic ototoxicity. These effects were increased by exposure to 16000 ppm toluene. Effects like those observed in Experiment 1 were noted on the FEP, but the oscillations were less with exposure to 16000 than 8000 ppm. Changes in the SEP were evident within 2 minutes of exposure onset, and amplitudes increased over the course of about 15 min, leveling off or decreasing thereafter. The amplitude of the N2P2 component was again less influenced than other components during exposure to 8000 ppm and was reduced to less than baseline amplitude by 16000 ppm. Effects of concentration and rates of development and recovery were systematically related to SEP component latency. Toluene appears to have both enhancing and inhibiting effects on neural pathways serving sensory systems, depending on the modality and the site of generation of the components within modalities. A particular balance between these properties might relate to the hedonic characteristics of this abused solvent.
在两项实验中，雄性Fischer-344大鼠通过吸入500、2000、5000、8000和16000 ppm甲苯暴露30分钟。在实验1中，高达8000 ppm的暴露导致了与浓度相关的咔嗒声诱发的脑干听觉诱发电位（CBAER）、闪光诱发电位（FEP）和体感诱发电位（SEP）变化。甲苯使CBAER成分的潜伏期延长，晚期成分的振幅增加。甲苯未检测到对FEP或SEP成分潜伏期的改变。早期FEP成分的振幅增加，晚期成分的振幅降低；甲苯还在FEP中诱发了刺激后振荡。SEP的大多数成分振幅大幅增加，但N2P2振幅似乎比其他成分对溶剂的抑制作用更敏感。在实验2中观察到了对CBAER的相同影响，但由短纯音诱发的晚期成分振幅有更显著的增加，这表明频率依赖性耳蜗刺激可能是先前观察到的亚慢性耳毒性的基础。暴露于16000 ppm甲苯会增强这些影响。在FEP上观察到了与实验1中类似的影响，但暴露于16000 ppm时的振荡比8000 ppm时少。暴露开始后2分钟内SEP就出现了明显变化，振幅在大约15分钟内增加，此后趋于平稳或下降。在暴露于8000 ppm时，N2P2成分的振幅再次比其他成分受影响小，而在16000 ppm时降低至低于基线振幅。浓度以及发育和恢复速率的影响与SEP成分潜伏期有系统的相关性。甲苯似乎对服务于感觉系统的神经通路既有增强作用又有抑制作用，这取决于感觉模式以及模式内成分的产生部位。这些特性之间的特定平衡可能与这种被滥用溶剂的享乐特性有关。
