PDF(Pubmed)
Abstract：
BACKGROUND: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
OBJECTIVE: 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.
METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
摘要：
背景：临床前研究报告，慢性乙醇暴露后乙醇诱导的条件性味觉厌恶（CTA）减弱，表明对乙醇的厌恶性产生了耐受性。然而,这些研究被预先暴露于无条件刺激(美国；乙醇)所混淆，这是众所周知的阻碍条件。
目的：本研究旨在确定在没有美国暴露前混淆的情况下，慢性乙醇暴露是否会产生对乙醇厌恶特性的耐受性。
方法：对成年雄性和雌性Long-Evans大鼠进行CTA，方法是将0.1%摄入的糖精与腹腔注射乙醇（1.5或2.0g/kg）或生理盐水配对。然后使用慢性间歇性乙醇（CIE）蒸气暴露使大鼠依赖乙醇。将对照暴露于室内空气(AIR)。蒸汽暴露后，检查了慢性乙醇对CTA表达和再调节的影响。
结果：在蒸汽暴露之前，两种性别的CTA水平相当，2.0g/kg产生的CTA高于1.5g/kg乙醇。蒸汽暴露后,与蒸汽前水平相比，空气对照显示CTA幅度增加。这种作用在暴露于CIE的大鼠中基本上不存在。在暴露于AIR和CIE的男性中，蒸气暴露后的再调节促进了CTA幅度的增加。相比之下,通过重新调节，女性的CTA幅度没有变化。
结论：这些数据表明，慢性乙醇不能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的孵育。CTA孵育的丧失表明CIE暴露破坏了编码厌恶的电路。
目的：本研究旨在确定在没有美国暴露前混淆的情况下，慢性乙醇暴露是否会产生对乙醇厌恶特性的耐受性。
方法：对成年雄性和雌性Long-Evans大鼠进行CTA，方法是将0.1%摄入的糖精与腹腔注射乙醇（1.5或2.0g/kg）或生理盐水配对。然后使用慢性间歇性乙醇（CIE）蒸气暴露使大鼠依赖乙醇。将对照暴露于室内空气(AIR)。蒸汽暴露后，检查了慢性乙醇对CTA表达和再调节的影响。
结果：在蒸汽暴露之前，两种性别的CTA水平相当，2.0g/kg产生的CTA高于1.5g/kg乙醇。蒸汽暴露后,与蒸汽前水平相比，空气对照显示CTA幅度增加。这种作用在暴露于CIE的大鼠中基本上不存在。在暴露于AIR和CIE的男性中，蒸气暴露后的再调节促进了CTA幅度的增加。相比之下,通过重新调节，女性的CTA幅度没有变化。
结论：这些数据表明，慢性乙醇不能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的孵育。CTA孵育的丧失表明CIE暴露破坏了编码厌恶的电路。
