Pearson B J, Donatelli D P, Freund R K, Palmer M R
Department of Pharmacology, University of Colorado Health Sciences Center, Denver 80262, USA.
J Pharmacol Exp Ther. 1997 Feb;280(2):739-46.
Rapid acute neuronal tolerance (RANT) to the depressant effects of ethanol (EtOH) is a desensitization of EtOH-induced depression of neuronal firing that develops over the first 5 to 7 min of EtOH exposure. This phenomenon has been hypothesized to play a role in acute behavioral insensitivity to EtOH and is expressed by cerebellar Purkinje neurons in animals selectively bred for insensitivity to EtOH-induced ataxia, such as low-alcohol-sensitive (LAS) rats and short-sleep mice. Purkinje neurons of animals bred for high sensitivity to EtOH-induced behavioral ataxia, such as high-alcohol-sensitive (HAS) rats and long-sleep mice, only infrequently express such acute tolerance to EtOH-induced depression of neuronal activity. However, because higher EtOH doses are required to depress Purkinje neuron activity in LAS rats than in HAS rats, it was not known whether the higher EtOH doses that depress LAS neurons would also induce RANT to EtOH in HAS rats, which were generally not exposed to such high EtOH doses in previous studies. Furthermore, the conditions for development and maintenance of RANT to EtOH had not been characterized. We found that RANT to EtOH-induced depression of cerebellar neurons principally developed within 5 min of EtOH application and recovered within 20 min of the last EtOH exposure and that neurons in HAS rats did not develop acute tolerance to the higher EtOH doses that were effective in LAS rats. We conclude that this rapid tolerance contributes to the acute EtOH sensitivity difference between LAS and HAS rats.
对乙醇（EtOH）抑制作用的快速急性神经元耐受（RANT）是指在接触EtOH的最初5至7分钟内，EtOH诱导的神经元放电抑制出现的脱敏现象。据推测，这一现象在对EtOH的急性行为不敏感中起作用，并且在因对EtOH诱导的共济失调不敏感而经选择性培育的动物的小脑浦肯野神经元中表现出来，比如低酒精敏感性（LAS）大鼠和短睡眠小鼠。而对EtOH诱导的行为性共济失调高敏感的动物，如高酒精敏感性（HAS）大鼠和长睡眠小鼠，其浦肯野神经元很少对EtOH诱导的神经元活动抑制表现出这种急性耐受。然而，由于抑制LAS大鼠浦肯野神经元活动所需的EtOH剂量高于HAS大鼠，因此尚不清楚抑制LAS神经元的较高EtOH剂量是否也会在HAS大鼠中诱导对EtOH的RANT，而在之前的研究中，HAS大鼠通常未接触过如此高剂量的EtOH。此外，对EtOH的RANT的发展和维持条件尚未明确。我们发现，对EtOH诱导的小脑神经元抑制的RANT主要在应用EtOH后的5分钟内形成，并在最后一次接触EtOH后的20分钟内恢复，并且HAS大鼠的神经元对在LAS大鼠中有效的较高EtOH剂量并未产生急性耐受。我们得出结论，这种快速耐受导致了LAS和HAS大鼠之间对EtOH急性敏感性的差异。
