Center for Alcohol Research in Epigenetics, Department of Psychiatry, University of Illinois at Chicago, 1601 W Taylor St, MC912, Chicago, IL, 60612, USA.
Psychopharmacology (Berl). 2024 Jun;241(6):1191-1203. doi: 10.1007/s00213-024-06553-5. Epub 2024 Feb 22.
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 largely absent in CIE-exposed rats. Re-conditioning after vapor exposure facilitated increased CTA magnitude to a similar degree in AIR- and CIE-exposed males. In contrast, CTA magnitude was unchanged by re-conditioning in females.
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,慢性乙醇暴露后,乙醇诱导的条件味觉厌恶(CTA)减弱,这表明对乙醇的厌恶特性产生了耐受性。然而,这些研究受到未暴露于条件刺激(US;乙醇)的混淆,众所周知,这会阻碍条件作用。
本研究旨在确定慢性乙醇暴露是否会在没有 US 预暴露混杂的情况下产生对乙醇的厌恶特性的耐受性。
通过将 0.1%摄入的蔗糖与腹腔内注射乙醇(1.5 或 2.0g/kg)或盐水配对,在成年雄性和雌性长耳大鼠中进行 CTA。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。对照动物暴露于室内空气(AIR)。在蒸气暴露后,检查慢性乙醇对 CTA 表达和再条件作用的影响。
在蒸气暴露之前,两性均以相当程度形成 CTA,2.0g/kg 乙醇产生的 CTA 大于 1.5g/kg 乙醇。蒸气暴露后,与暴露前水平相比,AIR 对照动物的 CTA 幅度增加。在 CIE 暴露的大鼠中,这种作用基本上不存在。蒸气暴露后再条件作用促进了 AIR 和 CIE 暴露雄性大鼠 CTA 幅度的同等程度增加。相比之下,雌性大鼠的 CTA 幅度不受再条件作用的影响。
这些数据表明,慢性乙醇不会促进对乙醇的厌恶特性的耐受性,而是减弱了乙醇诱导的 CTA 的潜伏期。CTA 潜伏期的丧失表明 CIE 暴露破坏了编码厌恶的回路。