Ramirez Lindsey A, Przybysz Kathryn R, Pitock Joseph R, Starr E Margaret, Yang Hyerim, Glover Elizabeth J
Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, Chicago, IL, USA.
bioRxiv. 2023 Sep 14:2023.09.13.557582. doi: 10.1101/2023.09.13.557582.
Preclinical studies report attenuated ethanol-induced conditioned taste aversion (CTA) following chronic ethanol exposure, suggesting that tolerance develops to the aversive properties of ethanol. However, these studies are confounded by pre-exposure to the unconditioned stimulus (US; ethanol), which is well known to hinder conditioning.
This study was designed to determine whether chronic ethanol exposure produces tolerance to the aversive properties of ethanol in the absence of a US pre-exposure confound.
CTA was performed in adult male and female Long-Evans rats by pairing 0.1% ingested saccharin with an intraperitoneal injection of ethanol (1.5 or 2.0 g/kg) or saline. Rats were then rendered ethanol dependent using chronic intermittent ethanol (CIE) vapor exposure. Controls were exposed to room air (AIR). The effect of chronic ethanol on CTA expression and reconditioning were examined following vapor exposure.
Prior to vapor exposure, both sexes developed CTA to a comparable degree with 2.0 g/kg producing greater CTA than 1.5 g/kg ethanol. Following vapor exposure, AIR controls exhibited an increase in CTA magnitude compared to pre-vapor levels. This effect was absent in CIE-exposed rats. These group differences were eliminated upon re-conditioning after vapor exposure.
These data suggest that chronic ethanol does not facilitate tolerance to the aversive properties of ethanol but rather, attenuates incubation of ethanol-induced CTA. Loss of CTA incubation suggests that CIE exposure disrupts circuits encoding aversion.
临床前研究报告称，长期乙醇暴露后，乙醇诱导的条件性味觉厌恶（CTA）减弱，这表明对乙醇的厌恶特性产生了耐受性。然而，这些研究因预先暴露于非条件刺激（US；乙醇）而混淆，众所周知，这会阻碍条件作用。
本研究旨在确定在不存在US预先暴露混淆因素的情况下，长期乙醇暴露是否会使机体对乙醇的厌恶特性产生耐受性。
通过将0.1%摄入的糖精与腹腔注射乙醇（1.5或2.0 g/kg）或生理盐水配对，在成年雄性和雌性Long-Evans大鼠中进行CTA实验。然后使用慢性间歇性乙醇（CIE）蒸气暴露使大鼠产生乙醇依赖性。对照组暴露于室内空气（AIR）中。在蒸气暴露后，检查慢性乙醇对CTA表达和重新条件作用的影响。
在蒸气暴露之前，两性均以相当的程度产生CTA，2.0 g/kg乙醇产生的CTA比1.5 g/kg乙醇更大。蒸气暴露后，AIR对照组的CTA幅度相较于蒸气暴露前有所增加。CIE暴露的大鼠中未出现这种效应。蒸气暴露后的重新条件作用消除了这些组间差异。
这些数据表明，长期乙醇暴露不会促进对乙醇厌恶特性的耐受性，而是会减弱乙醇诱导的CTA的潜伏期延长。CTA潜伏期延长的消失表明CIE暴露破坏了编码厌恶的神经回路。
