Sucrose fading and intermittent access are two common procedures that induce alcohol consumption in rodents. Sucrose fading procedures involve exposing ethanol naïve rats to a mixture of ethanol and sucrose and gradually reducing the concentration of sugar. Intermittent access procedures involve providing rats with access to ethanol on alternating days. Given that rats will consume ethanol without sucrose, the role of sugar in the sucrose fading procedure is unclear. Rats must be ethanol naïve when they are exposed to treatment with sucrose fading, so there is no point of comparison to show that exposure to sugar in sucrose fading produces higher levels of drinking. There has yet to be any work that isolates the effects of sugar on the consumption of alcohol. The purpose of the present experiment was to examine the effects of sucrose on ethanol consumption in rats with different alcohol histories. Two groups of six rats were exposed to two successive sucrose fading procedures, 30 days apart and their drinking was measured 30 days after each one. One group was exposed to an intermittent access procedure to establish drinking prior to treatment with sucrose fading, the other was ethanol naïve. Following sucrose fading, all rats drank pharmacologically active doses of ethanol. For both groups consumption correlated with the concentration of sucrose and decreased in a step-wise manner as it was faded. For the ethanol experienced rats, consumption dropped below baseline levels as sucrose was faded and decreased further with the second exposure. In contrast, the ethanol-naïve rats did not decrease consumption from the first sucrose fading procedure to the second. Slight differences in peak force of responses were also observed.

Alcohol consumption causes liver diseases, designated as Alcoholic Liver Disease (ALD). Because alcohol is detoxified by alcohol dehydrogenase (ADH), a major ethanol metabolism system, the development of ALD was initially believed to be due to malnutrition caused by alcohol metabolism in liver. The discovery of the microsomal ethanol oxidizing system (MEOS) changed this dogma. Cytochrome P450 enzymes (CYP) constitute the major components of MEOS. Cytochrome P450 2E1 (CYP2E1) in MEOS is one of the major ROS generators in liver and is considered to be contributive to ALD. Our labs have been studying the relationship between CYP2E1 and ALD for many years. Recently, we found that human CYP2A6 and its mouse analog CYP2A5 are also induced by alcohol. In mice, the alcohol induction of CYP2A5 is CYP2E1-dependent. Unlike CYP2E1, CYP2A5 protects against the development of ALD. The relationship of CYP2E1, CYP2A5, and ALD is a major focus of this review.