IntroductionInhalant abuse is an important health issue especially among children and adolescents who often encounter these agents in the home. Research into the neurobiological targets of inhalants has lagged behind that of other drugs such as alcohol and psychostimulants. However, studies from our lab and others have begun to reveal how inhalants such as the organic solvent toluene affect neurons in key addiction related areas of the brain including the ventral tegmental area, nucleus accumbens and medial prefrontal cortex. In the present study, we extend these findings and examine the effect of toluene on electrophysiological responses of pyramidal neurons in the basolateral amygdala BLA, a region important for generating emotional and reward based information needed to guide future behavior.MethodsWhole-cell patch-clamp electrophysiology recordings of BLA pyramidal neurons in rat brain slices were used to assess toluene effects on intrinsic excitability and excitatory glutamatergic synaptic transmission.ResultsAcute application of 3 mM but not 0.3 mM toluene produced a small but significant (~20%) increase in current-evoked action potential (AP) firing that reversed following washout of the toluene containing solution. The change in firing during exposure to 3 mM toluene was accompanied by selective changes in AP parameters including reduced latency to first spike, increased AP rise time and decay and a reduction in the fast after-hyperpolization. To examine whether toluene also affects excitatory synaptic signaling, we expressed channelrhodopsin-2 in medial prefrontal cortex neurons and elicited synaptic currents in BLA neurons via light pulses. Toluene (3 mM) reduced light-evoked AMPA-mediated synaptic currents while a lower concentration (0.3 mM) had no effect. The toluene-induced reduction in AMPA-mediated BLA synaptic currents was prevented by the cannabinoid receptor-1 antagonist AM281.DiscussionThese findings are the first to demonstrate effects of acute toluene on BLA pyramidal neurons and add to existing findings showing that abused inhalants such as toluene have significant effects on neurons in brain regions involved in natural and drug induced reward.

中文翻译：

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甲苯改变基底外侧杏仁核神经元的内在兴奋性和兴奋性突触传递

简介吸入滥用是一个重要的健康问题，特别是对于经常在家中接触这些物质的儿童和青少年而言。对吸入剂神经生物学目标的研究落后于酒精和精神兴奋剂等其他药物。然而，我们实验室和其他实验室的研究已经开始揭示有机溶剂甲苯等吸入剂如何影响大脑中与成瘾相关的关键区域的神经元，包括腹侧被盖区、伏核和内侧前额皮质。在本研究中，我们扩展了这些发现，并检查了甲苯对基底外侧杏仁核 BLA 中锥体神经元电生理反应的影响，该区域对于生成指导未来行为所需的基于情感和奖励的信息非常重要。方法全细胞膜片钳电生理学使用大鼠脑切片中 BLA 锥体神经元的记录来评估甲苯对内在兴奋性和兴奋性谷氨酸突触传递的影响。结果急性应用 3 mM（而非 0.3 mM）甲苯会产生小但显着 (~20%) 的电流诱发作用增加潜在（AP）点火在冲洗含甲苯的溶液后逆转。暴露于 3 mM 甲苯期间放电的变化伴随着 AP 参数的选择性变化，包括减少第一次尖峰的潜伏期、增加 AP 上升时间和衰减以及快速后超极化的减少。为了检查甲苯是否也会影响兴奋性突触信号传导，我们在内侧前额叶皮层神经元中表达通道视紫红质-2，并通过光脉冲在 BLA 神经元中引发突触电流。甲苯 (3 mM) 可减少光诱发的 AMPA 介导的突触电流，而较低浓度 (0.3 mM) 则没有效果。甲苯诱导的 AMPA 介导的 BLA 突触电流减少被大麻素受体 1 拮抗剂 AM281 阻止。讨论这些发现首次证明了急性甲苯对 BLA 锥体神经元的影响，并补充了现有的发现，表明滥用吸入剂（例如甲苯）对涉及自然和药物诱导奖励的大脑区域的神经元有显着影响。