Comparative characteristics of voluntary and semivoluntary methods of the alcoholization of rats

Water and ethanol consumption, blood and urine ethanol concentrations were measured in male rats aged 1.5 to 8 months. The animals had ethanol solutions (5-25%) and water as alternate fluid (two-bottle choice) or a 10% ethanol solution as a sole water source. In both cases, the rats did not exceed 7 g/kg of ethanol consumption per day. From 10 a.m. to 16 p.m. the blood ethanol concentration was no more than 0.1 g/l. Ethanol excretion with urine did not go beyond 0.1% of the daily dose. Ethanol consumption was increased by 1-2 g/kg a day if saccharin (0.125%) and sodium chloride (1%) were added to ethanol solution. In this case the withdrawal signs developed after ethanol consumption cessation.     

Flavor preferences conditioned by intragastric ethanol with limited access training

In a prior study, ad libitum fed rats learned a strong preference (90%) for a flavored saccharin solution (conditioned stimulus, CS+) paired with concurrent intragastric (IG) infusions of 5% ethanol over another flavor (CS-) paired with water infusions in unlimited access sessions (22 h/day). The present study expanded the investigation of ethanol-conditioned preferences to limited access sessions (30 min/day). Experiment 1 revealed that ad lib or food-restricted rats failed to develop a CS+ preference using the same CS solutions (0.05% Kool-Aid+0.2% saccharin) and IG infusions that were effective with long-term training. Experiments 2 and 3 mimicked the parameters from a report of successful ethanol conditioning in deprived rats: ethanol (0.5 g/kg) or water was infused intragastrically 5 min before access to sweetened CS solutions flavored with HCl or NaCl. Rats learned to prefer the ethanol-paired CS+ when the flavors were mixed with 5% sucrose but not when mixed with 0.2% saccharin. Experiment 4 revealed that 5% sucrose solutions flavored with 0.25% Kool Aid also supported flavor preference conditioning by IG ethanol (0.5 g/kg). CS+ preferences were obtained in rats trained with ethanol infused 5 min before or concurrent with CS+ intake, but not in rats trained with ethanol infused 30 min before CS+ intake. These data confirm that flavor preferences can be conditioned by IG ethanol using a limited access procedure. However, in contrast to 22 h/day training, 30 min/day training requires more intense CS flavors and a nutritive sweetener. The preference reinforcing actions of ethanol may develop slowly and are thus most effective with long training sessions or when intense CS flavors are used in short training sessions.     

Differences in response to the aversive properties of ethanol in rats selectively bred for oral ethanol preference

A conditioned taste aversion (CTA) paradigm was used to determine whether aversion to the pharmacological effects of ethanol, apart from orosensory cues, can contribute to genetic differences in voluntary ethanol consumption. Four doses of ethanol, administered IP, were paired with the consumption of a 0.1% saccharin solution in rats from the alcohol-preferring (P) and alcohol-nonpreferring (NP) lines. Repeated pairing of saccharin and ethanol in a dose of 1.0 g/kg produced stronger and more prolonged aversion to saccharin in NP rats, compared with P rats, at comparable blood ethanol levels. A low dose of ethanol (0.25 g/kg) produced transient conditioned facilitation of saccharin consumption in P rats, but not in NP rats, at comparable blood ethanol levels. The results suggest that rats of the NP line find the postingestional effects of high-dose ethanol more aversive, and low-dose ethanol less reinforcing, than do rats of the P line. Genetic differences in voluntary ethanol consumption may be due, in part, to differences in aversion to the postingestional effects of ethanol.     

The High-Ethanol Preferring rat as a model to study the shift between alcohol abuse and dependence

The High-Ethanol Preferring line of rats (HEP), recently selected by R.D. Myers, is characterised by a high voluntary consumption of alcohol (3-4 g/kg/day for males and 6-8 g/kg/day for females, when a 10% ethanol solution is available as a choice vs. water) and a high sensitivity to taste reinforcement (saccharin, quinine). Our previous data obtained with HEP rats showed no evidence of development of dependence after long-term sustained alcohol intake. In this study, we subjected these rats to several long-term administration protocols suggested to favour the development of alcohol dependence, including multiple alcohol concentrations or sweetened alcohol solutions (ethanol 10% or 20%+saccharin), and deprivation periods. The results showed no increase in alcohol consumption, no shift of preference for alcohol solutions when offered as a free choice vs. a preferred saccharin solution, and a very limited alcohol-deprivation effect when alcohol is made available after a period of deprivation, the three criteria used to demonstrate the development of dependence. Regardless of the method used, HEP rats failed to show dependence after long-term, heavy ethanol consumption. Resistance to ethanol dependence may in fact be genetically influenced and the HEP rat appears as a valuable model to search for factors involved in the transition from alcohol abuse to dependence.     

Effect of addition of ethanol and NaCl on saccharin + glucose polydipsia.

Rats received an ad lib choice of food, water, and a solution containing saccharin, glucose, and NaCl solutes either as single stimuli or in combinations. Ethanol was gradually added to these vehicles or water from 0.5--15% w/v. Ethanol intakes of all groups with vehicles containing glucose were higher than intakes of the water vehicle group. Ethanol intakes of the 0.125% saccharin + 3.0% glucose + 1.0% NaCl + ethanol group were highest, peaking at greater than 9.0 g/kg/day, and this group displayed the highest blood ethanol levels. However, there was no evidence of withdrawal syndrome, nor of increased intake of unflavored ethanol by groups previously receiving flavored ethanol. It is suggested that ethanol eliminative capacity limits free-choice ethanol intake when maximized by the addition of sapid congeners.     

The induction of oral ethanol self-administration by contingent ethanol delivery

The necessity of delivering a highly reinforcing stimulus (20% sucrose) contingent upon ethanol consumption in order to induce ethanol self-administration in free-feeding rats was investigated. Rats water deprived for 12-16 h were placed in an environment in which ethanol drinking resulted in the presentation of ethanol. This procedure was successful in inducing and maintaining ethanol self-administration over concentrations of 5-20% (v/v). Compared to a group of rats initially reinforced for drinking ethanol with sucrose presentation, contingent ethanol delivery resulted in greater ethanol self-administration behavior. When 20% ethanol was available the group trained with ethanol had average intake of 0.91 g/kg, whereas the group trained with sucrose had a mean intake of 0.69 g/kg in a 30-min session. The results suggest that ethanol's reinforcing properties are sufficient to establish ethanol self-administration within the context of the inducing environment.     

Flavor preferences conditioned by intragastric infusion of ethanol in rats

Sprague-Dawley rats were trained 22 h/day to associate a flavored solution [conditioned stimulus (CS+)] with intragastric infusions of 6% ethanol and another flavored solution (CS-) with water infusions. The infusions were matched to the CS intakes so that the animals determined their timing and size. In Phase 1, chow and water were available ad libitum, and both CS flavors were initially sweetened with saccharin that was then faded out. The rats displayed a preference for the CS+ over the CS- under both reinforced and extinction conditions. When food-restricted in Phase 2, the rats displayed an increased preference for the CS+. In Phase 3, the rats were fed ad libitum chow and given preference tests with the CS+ paired with ethanol infusions of increasing concentration (6%, 12%, 18%, and 24%). Their preference for the CS+ over the CS- persisted, and self-administered ethanol dose increased with concentration to 5 g/kg/day. The ethanol-based conditioned flavor preference resembled those conditioned by carbohydrate and fat infusions, suggesting that at least some of reinforcing ability of ethanol may be related to its postingestive nutritive effects.     

Maternal ethanol consumption by pregnant guinea pigs causes neurobehavioral deficits and increases ethanol preference in offspring

The objective of this study was to test the hypothesis that prenatal exposure to ethanol, through maternal consumption of an aqueous ethanol solution, induces neurobehavioral deficits and increases ethanol preference in offspring. Pregnant Dunkin-Hartley-strain guinea pigs were given 24-h access to an aqueous ethanol solution (5%, v/v) sweetened with sucralose (1 g/l), or water sweetened with sucralose (1 g/l), throughout gestation. Spontaneous locomotor activity was measured in the offspring on postnatal day (PD) 10. The offspring underwent either ethanol preference testing using a two-bottle-choice paradigm beginning on PD 40 or Morris water maze testing using a hidden moving platform design beginning on PD 60. Maternal consumption of a 5% (v/v) ethanol solution (average daily dose of 2.3±0.1 g of ethanol/kg maternal body weight; range: 1.8-2.8 g/kg) decreased offspring birth weight, increased spontaneous locomotor activity, and increased preference for an aqueous ethanol solution. In the Morris water maze test, sucralose-exposed offspring decreased escape latency on the second day of testing, whereas the ethanol-exposed offspring showed no improvement. These data demonstrate that moderate maternal consumption of ethanol produces hyperactivity, enhances ethanol preference, and impairs learning and memory in guinea pig offspring.     

Ro 15-4513 selectively attenuates ethanol,but not sucrose,reinforced responding in a concurrent access procedure: comparison to other drugs

The experiments described in this report used a concurrent access procedure to study ethanol reinforcement. Rats were trained to lever press for a 10% sucrose solution and a 10% ethanol/10% sucrose mixture, and both reinforcers were available on variable-interval 5-s schedules. In baseline and vehicle injection sessions, the animals distributed their responding between both solutions. When injected with the partial inverse benzodiazepine agonist Ro 15-4513 (3, 9, and 18 mg/kg), responding for the ethanol solution decreased while responding for sucrose remained intact. Ethanol injections (0.5 and 1.0 g/kg) engendered a similar profile. Chlordiazepoxide led to an increase in ethanol mix responding at 2 mg/kg and a decrease in ethanol mix responding at higher doses; no dose affected sucrose responding. Morphine (0.5–16 mg/kg) decreased responding for both the ethanol mix and sucrose solutions, more or less simultaneously. Naloxone (0.125–20 mg/kg) selectively reduced ethanol mix responding at low doses, and decreased responding for both reinforcers at high doses. In another group of animals, isocaloric alternatives were concurrently available: 10% ethanol/0.25% saccharin versus 14% sucrose. Injections of Ro 15-4513 and chlordiazepoxide produced similar results as in the first group of rats: an increase in ethanol mix responding with low dose chlordiazepoxide, and a decrease in ethanol mix responding with Ro 15-4513. However, naloxone injections did not selectively affect responding for either of the reinforcers when they were isocaloric. These results are discussed in terms of ethanol's neuropharmacological actions.     

Combined effects of buprenorphine and a nondrug alternative reinforcer on IV cocaine self-administration in rats maintained under FR schedules

Although previous studies have shown that pharmacological agents, such as buprenorphine, and alternative nondrug reinforcers, such as money or sweetened solutions, reduce cocaine self-administration, few studies have examined the combined effects of these two approaches. The purpose of the present study was to evaluate the effects of the opioid partial agonist buprenorphine (0.1 mg/kg) and concurrent access to either water or a glucose plus saccharin solution (G+S, 3% and 0.125% wt/vol) in rats self-administering intravenous (IV) cocaine (0.4 mg/kg per infusion) under fixed-ratio schedules (FR2, 8 or 32). One group had concurrent access to water and another group had concurrent access to G+S. After 3 consecutive days of stable cocaine self-administration, a single buprenorphine injection (0.1 mg/kg IV) was administered 30 min before the start of the experimental session for 3 consecutive days. To summarize the results, (1) the presence of an alternative non-drug reinforcer significantly reduced cocaine self-administration; (2) buprenorphine selectively decreased cocaine, but not water or G+S, self-administration; (3) the decrease in cocaine infusions by buprenorphine was greatest on the first day of buprenorphine administration; and (4) expressed as a percentage of baseline conditions, the combination of buprenorphine and G+S produced a greater decrease in cocaine self-administration than either buprenorphine or G+S alone. These results indicate that combined treatment with buprenorphine and concurrent access to a sweetened solution is a more effective strategy for reducing cocaine self-administration than either strategy alone.     

Total avoidance of saccharin consumption by rats after repeatedly paired injections of ethanol or LiCl

Rats injected with ethanol or LiCl following consumption of novel saccharin solution drank less saccharin than non-poisoned controls on a subsequent exposure with degree of aversion positively related to dose of ethanol (2–5 g/kg). While a single pairing of saccharin with ethanol or LiCl resulted in partial avoidance of saccharin,solution, repeated conditioning trials led to total avoidance of saccharin consumption by animals injected with the higher doses of ethanol or with LiCl. These results, characteristic of emetic-induced aversions, support the explanation of the limited consumption of ethanol by rats under ad lib, free-choice conditions as a result of acquired aversion to the oronasal sensory stimuli of ethanol after association with pharmacologically aversive aftereffects of consumed ethanol.     

Oral self-administration of sweetened nicotine solutions by rats

Oral self-administration of sweetened nicotine solutions in rats was studied in two ways. In the first experiment, one group had continuous access to a water bottle containing a sucrose solution and nicotine (10 μg/ml), while another group had access to an identical sucrose solution without nicotine. All rats had continuous access to water. While consumption of nicotine increased with increasing concentrations of sucrose, consumption of the sucrose + nicotine solution never exceeded the intake of sucrose alone. In subsequent experiments, the delivery of the solutions was made contingent upon an operant response. The sucrose + nicotine solution was found to maintain responding to higher response/reinforcer ratiosthan the sucrose only solution. These data demonstrate that rats will self-administer sweetened nicotine solutions and that sucrose + nicotine solutions are more reinforcing than sucrose solutions alone. Free accessconsumption is not a good predictor of the response maintaining properties of nicotine solutions.     

Repeated binge ethanol administration during adolescence enhances voluntary sweetened ethanol intake in young adulthood in male and female rats

Binge alcohol consumption is a rising concern in the United States, especially among adolescents. During this developmental period alcohol use is usually initiated and has been shown to cause detrimental effects on brain structure and function as well as cognitive/behavioral impairments in rats. Binge models, where animals are repeatedly administered high doses of ethanol typically over a period of three or four days cause these effects. There has been little work conducted aimed at investigating the long-term behavioral consequences of repeated binge administration during adolescence on later ethanol-induced behavior in young adulthood and adulthood. The repeated four-day binge model may serve as a good approximate for patterns of human adolescent alcohol consumption as this is similar to a “bender” in human alcoholics. The present set of experiments examined the dose-response and sex-related differences induced by repeated binge ethanol administration during adolescence on sweetened ethanol (Experiment 1) or saccharin (Experiment 2) intake in young adulthood. In both experiments, on postnatal days (PND) 28-31, PND 35-38 and PND 42-45, ethanol (1.5, 3.0 or 5.0 g/kg) or water was administered intragastrically to adolescent rats. Rats underwent abstinence from PND 46-59. Subsequently, in young adulthood, ethanol and saccharin intake were assessed. Exposure to any dose of ethanol during adolescence significantly enhanced ethanol intake in adulthood. However, while female rats had higher overall g/kg intake, males appear to be more vulnerable to the impact of adolescent ethanol exposure on subsequently increased ethanol intake in young adulthood. Exposure to ethanol during adolescence did not alter saccharin consumption in young adulthood in male or female rats. Considering that adolescence is the developmental period in which ethanol experimentation and consumption is usually initiated, the present set of experiments demonstrate the importance of elucidating the impact of early binge-pattern ethanol exposure on the subsequent predisposition to drink later in life.     

Flavor quality and ethanol concentration affect ethanol-conditioned flavor preferences

A previous report showed that outbred rats acquired preferences for a sweetened conditioned stimulus (CS) flavor paired with intragastric ethanol. To evaluate the role of sweet taste in ethanol conditioning, this study compared training with sweetened and unsweetened flavors. In Experiment 1, nondeprived rats were trained to drink one flavored solution (CS+, e.g., grape) paired with intragastric infusion of 5% ethanol and another (CS-, e.g., cherry) paired with intragastric water on alternate days. The volume of ethanol solution infused was matched to the volume of flavored solution the rats consumed. The sweet group's flavors initially contained 0.2% saccharin, reduced to 0.1%, 0.05%, and 0% over days; the plain group's flavors were unsweetened. The sweet group drank more and self-infused more ethanol during training and its preference for the CS+ over the CS- (without saccharin) exceeded that of the plain group (75% versus 62%). Experiment 2 equated total ethanol intake in rats trained with two combinations of flavor quality and ethanol concentration. The Sweet5 group drank flavors with 0.2% saccharin throughout training and tests and received 5% ethanol when they drank CS+, while the Plain10 group drank unsweetened flavors and the CS+ was paired with 10% ethanol. Despite equal daily ethanol doses, the Sweet5 group strongly preferred the CS+ (89%) while the Plain10 group avoided it (31%). The two groups continued to show opposite CS+ preference profiles even when both were tested with sweet CS flavors and 10% ethanol infusions. Thus, sweet taste contributes to the development of ethanol-conditioned flavor preferences, and this effect is not explained by a simple enhancement of ethanol intake.     

Reduced alcohol drinking in adult rats exposed to sucrose during adolescence

Intake of sweet-alcoholic drinks during adolescence is believed to favor alcohol abuse and dependence in adulthood. This study examined the influence of early exposure to ethanol with or without sucrose on the consumption of sweet or alcoholic solutions in adulthood. Adolescent rats (from post-natal day 30-46) were given continuous free access to tap water and either 5% sucrose, 5% ethanol or mixed 5% sucrose-5% ethanol. The control group was given access to water only. Upon reaching adulthood (post-natal day 60), rats were tested for saccharin (sweet), quinine (bitter) and ethanol consumption using a two-bottle free-choice paradigm. The results indicated that pre-exposure to ethanol did not alter the intake of sweet or ethanol solutions in adulthood. However, rats exposed to sucrose during adolescence showed a decreased consumption of both sweet and ethanol solutions. Because alcohol has a sweet taste component, an additional group of rats, pre-exposed to either 5% sucrose or water during adolescence, was tested for intravenous ethanol self-administration (preventing oral sensory stimulation) and in a new model of simultaneous access to oral saccharin and intravenous ethanol that results in higher total ethanol intake. Relative to controls, sucrose-exposed rats showed reduced operant self-administration of saccharin, yet no differences were found for intravenous ethanol self-administration. Altogether, these findings indicate that sucrose exposure during adolescence persistently affected the perception of sweet taste reward and thereby alcohol’s acceptance in adulthood.     

Brain ethanol levels in rats after voluntary ethanol consumption using a sweetened gelatin vehicle

A novel procedure for initiation of voluntary ethanol consumption in the rat was evaluated in terms of ease of initiation, consistency, and resulting brain ethanol levels. The "jello shot" consists of 10% ethanol in gelatin along with a caloric source (Polycose). Initiation of "jello shot" consumption in Sprague-Dawley rats required no food or water restriction and resulted in initial daily (8.4+/-0.6 g/kg body weight) and eventual hourly (1.1+/-0.1 g/kg body weight) intake of ethanol comparable to other procedures using either alcohol-preferring or non-genetically selected rats. Rat intake of ethanol via "jello shots" recovered quickly from environmental alterations and surgical implantation of a guide cannula. During 1-h free access sessions, consumption of the "jello shot" occurred during the initial 10 min and resulted in a dose-related increase in ethanol levels in nucleus accumbens measured using microdialysis. These brain ethanol levels were comparable to those achieved using other self-administration methods. However, when 0.5 g/kg ethanol was gavaged either in "jello shot" or saline, there was about a 20% decrease in brain ethanol concentrations after gavage of the "jello shot" compared to saline. Even so, lack of a need for initial food or water deprivation and the rapidity with which stable self-administration can be achieved both suggest utility of the "jello shot" as a completely voluntary ethanol procedure.     

Oral drug self-administration in the home cage of mice: alcohol-heightened aggression and inhibition by the 5-HT1B agonist anpirtoline

RATIONALE: In order to model heightened aggression after alcohol consumption and to study the inhibitory influence of 5-HT1B receptors on drinking and fighting, an experimental procedure should enable self-administration of precise amounts of alcohol in a limited period of time before an aggressive confrontation. OBJECTIVES: To design a new device that can reinforce operant responding by the delivery of sweet alcohol in the resident mouse home cage, where aggressive behavior toward an intruder can subsequently be examined, and to demonstrate inhibition of alcohol-heightened aggression by 5-HT1B receptor agonist treatment. METHODS: Within one experimental session, all singly housed CFW male mice (n=26) performed a nose-poke response that was reinforced by 0.05 ml sucrose. Using the sucrose fading technique, eventually the mice consumed a 6% ethanol/4% sucrose solution after each fifth nose poke during daily 15-min experimental sessions. The number of ethanol reinforcements was adjusted so that 0.6, 1.0, 1.7, and 3.0-g/kg doses were consumed in 15 min or less. Assays confirmed blood alcohol levels at 68.1 mg/dl for intake of 1.0 g/kg. After consuming a specific dose of ethanol in the form of a fixed number of response-dependent deliveries, the response panel was removed from the home cage and, 15 min later, the resident confronted a male intruder. Anpirtoline was administered either before alcohol self-administration or before the aggressive confrontation. RESULTS: After being reinforced with 1.0 g/kg or 1.7 g/kg sweet ethanol, the mice significantly increased attack and threat behavior relative to their aggressive behavior following sucrose or water consumption only. Treatment with the 5-HT1B receptor agonist anpirtoline (0.125, 0.25, 0.5 mg/kg, i.p.) before the confrontation decreased alcohol-heightened aggression and species-typical aggression in the absence of changes in other elements of the behavioral repertoire. Anpirtoline affected ethanol-reinforced behavior only at doses that were 5-10 times higher than those producing anti-aggressive effects. CONCLUSIONS: Self-administration of alcohol in the home cage of mice is readily accomplished with the aid of a simple, removable panel. The effective inhibition of high levels of aggressive behavior due to alcohol consumption after anpirtoline treatment confirm the 5-HT1B receptor as a critical site in the termination of aggression.     

Effects of bromocriptine on self-administration of sweetened ethanol solutions in rats

The effect of bromocriptine (BRO), a D₂ receptor agonist, on chronic oral ethanol (ETOH) self-administration was tested in a home-cage environment. Male Wistar rats (n = 77) were food deprived for 24 h. Then, a period of 15 days of limited-access (1h/day) to food and to a sweetened ETOH solution was started [3% w/v of glucose and several concentrations of ETOH depending upon the group: 0% (control group), 1.5%, 5% or 10% v/v]. Later, another period started in which rats were maintained in a free-choice, two-bottle situation with food, tap-water and the sweetened solution available for 24 h/day, for 14 days. Following this period, BRO (5 mg/kg, SC) was administered, once daily, for 5 days, in the same continuous free-access conditions. ETOH consumption was also studied for 4 days after the last BRO injection. BRO increased ETOH self-administration throughout the 5-day period, regardless of the ETOH concentration available, in the rats with previous higher ETOH intake, without effect in the control animals. In the control rats, water intake was increased, whereas in the group that had access to the lowest ETOH concentration a decrease in water consumption was found. The enhanced ETOH drinking was maintained after BRO treatment for the animals with previous higher ETOH intake. BRO effects on water consumption were also maintained. These data suggest that BRO can potentiate ETOH intake and provide further support for the role of dopamine (DA) systems in mediating volitional oral intake of ETOH. Received: 25 January 1996 / Final version: 12 June 1996     

Zonisamide decreases ethanol intake in rats and mice

Several anticonvulsant agents, including topiramate and valproate, have been found to reduce alcohol consumption in rodent models of drinking. The question of whether the novel anticonvulsant agent, zonisamide, shares similar actions in either mice or rats was investigated in the present experiments. In an initial experiment, the consumption of a 10% ethanol-5% sucrose solution, available for one hour, by Wistar rats treated with lactose, topiramate, or zonisamide was determined. In a second experiment, the intake of a 10% ethanol/water solution, accessible for two hours, by C57BL/B6N mice treated with either zonisamide or vehicle was assessed. In the rat, 50 mg/kg (PO) doses of either topiramate or zonisamide produced significant, but moderate decreases in ethanol/sucrose intake. The administration of a 50 mg/kg (IP) dose of zonisamide to mice resulted in a marked lowering in ethanol consumption. These results provide evidence that zonisamide administration will decrease ethanol consumption by both mice and rats in limited access models of drinking, and might, like topiramate, be useful as a medication for alcoholism.     

Erucine suppresses ethanol intake and preference in alcohol-preferring Fawn-Hooded rats

Aim： Brucine （BRU） extracted from the seeds of Strychnos nux-vomica L is glycine receptor antagonist. We hypothesize that BRU may modify alcohol consumption by acting at glycine receptors, and evaluated the pharmacodynamic profiles and adverse effects of BRU in rat models of alcohol abuse. Methods： Alcohol-preferring Fawn-Hooded （FH/Wjd） rats were administered BRU （10, 20 or 30 mg/kg, sc）. The effects of BRU on alcohol consumption were examined in ethanol 2-bottle-choice drinking paradigm, ethanol/sucrose operant self-administration paradigm and 5-d ethanol deprivation test. In addition, open field test was used to assess the general locomotor activity of FH/Wjd rats, and conditioned place preference （CPP） was conducted to assess conditioned reinforcing effect. Results： In ethanol 2-bottle-choice drinking paradigm, treatment with BRU for 10 consecutive days dose-dependently decreased the ethanol intake associated with a compensatory increase of water intake, but unchanged the daily total fluid intake and body weight. In ethanol/sucrose operant self-administration paradigms, BRU （30 mg/kg） administered before each testing session significantly decreased the number of lever presses for ethanol and the ethanol intake, without affecting the number of sucrose （10%） responses, total sucrose intake, and the number of lever presses for water. Acute treatment with BRU （30 mg/kg） completely suppressed the deprivation-induced elevation of ethanol consumption. Treatment with BRU （10, 20, and 30 mg/kg） did not alter locomotion of FH/Wjd rats, nor did it produce place preference or aversion. Conclusion： BRU selectively decreases ethanol consumption with minimal adverse effects. Therefore, BRU may represent a new pharmacotherapy for alcoholism.