Proportion Of Ethanol Research Articles

Voltammetric behavior and determination of tocopherols with partial least squares calibration: analysis in vegetable oil samples

The voltammetric behavior of Vitamin E in the presence of olive oil is studied at the glassy carbon electrode, in a hexane–ethanol medium, with diverse techniques: sampled DC, differential pulse, and square-wave voltammetry. The influence of such variables as the hexane–ethanol proportion, sulfuric acid concentration, and instrumental parameters is studied. Separate voltammetric peaks are obtained for α-tocopherol and δ-tocopherol, but the peaks for β-tocopherol and γ-tocopherol overlap. For the simultaneous determination of α-, β+γ-, and δ-tocopherols in vegetable oils by the PLS-1 multivariate calibration method, the results using sampled DC and DPV voltammograms are compared. The DPV voltammograms are found to be the best data set. The proposed method is applied to the determination of the tocopherols in different vegetable oil samples. The olive oil samples needed a prior cleaning stage by solid-phase extraction on silica cartridges. The results are very acceptable.

Uronic (hexenuronic) acid profile of ethanol–alkali delignification of giant reed Arundo donax L.

The effect of process variables on uronic acids (UAs) and hexenuronic acids (HexAs) in the annual crop Arundo donax L. during ethanol–alkali pulping has been examined. A substantial loss of UA moieties (up to 90%) was observed by the end of pulping (target kappa number 18) performed with 25% NaOH and 40% EtOH (by volume) within the temperature range of 130–150 °C. At the same time, the progressive formation of HexA in pulp was detected from the early phases of delignification. The proportion of HexA in the residual UA of the final pulp was found to be 84%, indicating almost complete conversion of 4-O-methylglucuronic acid side groups (MeGlcA) of heteroxylan into HexA. The kinetics of UA degradation and HexA formation has been described in terms of three consecutive first-order reaction stages. The overall rate of UA degradation was one order higher than the rate of UA conversion into HexA. The values of apparent activation energy were estimated as 68.6 and 94.7 kJ mol−1, respectively. The reaction medium alkalinity was shown to be the controlling factor for UA and HexA stability during ethanol–alkali pulping. An increase in alkali charge from 5% to 35% (as NaOH) led to UA loss of 40%, but promoted HexA formation from 11.8 to 20.1 μmol g−1. The addition of organic solvent to the alkaline pulping solution had a similar effect, and about 10% of UA was lost and the content of HexA increased from 6.9 to 10.9 μmol g−1 with an increase in ethanol proportion in the liquor from 20% to 60%.

Crystalline swelling of organo-modified clays in ethanol–water solutions

The swelling of organo-modified clays in organic solvents may have important consequences on bulk properties of materials based on this technology. X-ray powder diffraction was used to study the swelling of orientated films of dioctahedral smectites exchanged with benzyloctadecyldimethylammonium (BODMA) cations, when equilibrated in ethanol–water solutions. The influence of total layer charge and the location of the layer charge on swelling of two organo-modified bentonites and three organo-modified reference smectites in ethanol–water solutions were evaluated. The measured interlayer spaces of BODMA smectites equilibrated in water increased with total layer charge and with the relative amount of tetrahedral charge. At intermediate ethanol concentrations, a distinct plateau was observed in the swelling profiles of BODMA smectites having layer charges >0.8 e − per O 20(OH) 4. When equilibrated in ethanol, all BODMA smectites expanded to similar values (34–36 Å). The magnitude of the change in crystalline swelling of organo-smectites in ethanol compared to that in water was found to be inversely proportional to total layer charge density but proportional to the ratio of octahedral to tetrahedral layer charge. Calculations using NEWMOD showed that the d-spacings measured were unlikely to be due to interstratifications of fully water-solvated with fully ethanol-solvated BODMA smectite layers. Introduction of up to 2.0 M aqueous NaCl resulted in a slight (∼0.5 Å) decrease in the interlayer spacing of BODMA montmorillonite. However, 0.02 and 0.2 M NaCl added to ethanol–water mixtures enhanced interlayer expansion in these miscible solvents. The results suggest that inorganic salt depressed the activity of water in ethanol–water mixtures and thereby increased the proportion of ethanol actually penetrating the interlayer spaces of BODMA smectites. A plausible mechanism is discussed to describe the observed interlayer expansion in ethanol–water solutions and how this might impact possible applications.

Effect of Formulation and Process Variables on the Release Behavior of Amoxicillin Matrix Tablets

The sustained release of amoxicillin is desired to be confined to the upper gastrointestinal tract to treat certain kind of infections. In vitro dissolution, at pH 1.2, of amoxicillin sustained release tablets has been studied varying the proportion of Carbopol 971P NF and sodium alginate as well as the ethanol/water proportion in the granulation fluid. Mt, the amount of drug released at time (t) and defined in terms of the total drug released over a long time period (Minf), was described by Mt/Minf = ktn. Matrices with increasing proportions of sodium alginate showed increasing values of the exponent indicative of the release mechanism (n) and increasing release constant values (k). This is attributed to a drop in the coherence of the polymeric matrix with increasing alginate proportions that produces an increasing polymer relaxation and erosion. Decreasing Carbopol 971P NF proportions reduce the amount of dissolved polymer during granulation, producing a lesser obstruction of amoxicillin dissolution. Alginate proportions of 80% produce near zero order release profiles. Granules obtained with increasing ethanol proportions showed increasing release constant values and a minor change in the exponent (n) values. This is considered a result of lower polymer dissolution during granulation that allows a lesser matrix coherence and a greater amoxicillin dissolution. Alginate matrices granulated with different ethanol/water proportions showed no significant changes in the amoxicillin release profile. There is a trend toward increasing floating times with increasing Carbopol 971P NF proportions.

Changes in neutral and malonyl ginsenosides in American ginseng ( Panax quinquefolium) during drying, storage and ethanolic extraction

Changes in the neutral and malonyl ginsenosides of American ginseng roots ( Panax quinquefolium) were examined during drying, storage and extraction. Freshly harvested roots dried at 40, 55 or 70 °C in a hot air drier showed a marked decrease in the time taken to dry as the air temperature increased but the colour of roots dried at 70 °C was darker than the desired cream colour. Increasing the drying temperature decreased the concentration of total ginsenosides but with an increase in the neutral ginsenosides and a decrease in malonyl ginsenosides. Dried root powder, stored at 5, 20 and 30 °C in air of low humidity, showed a decrease in the concentration of total ginsenosides at all temperatures with the rate of loss increasing at higher temperatures. The concentration of malonyl ginsenosides showed the same trend but the concentration of neutral ginsenosides did not significantly change during storage at any temperature. Extraction of ginsenosides, from dried root powder with aqueous ethanol, varied with the ethanol content. Maximum extraction of neutral ginsenosides was obtained with 70% ethanol while, for malonyl ginsenosides, it was 40% ethanol and 60% ethanol for total ginsenosides. The ratio of neutral to malonyl ginsenosides in the extract increased as the proportion of ethanol in the solvent increased. The findings show that the relative proportions of neutral and malonyl ginsenosides vary considerably during postharvest handling and reinforce the need to measure both types to obtain the true level of total ginsenosides.

Influence of ethanol content on the extent of copigmentation in a cencibel young red wine.

The effect of ethanol content on the copigmentation of a Cencibel young red wine was studied, by means of ethanol elimination and reconstitution of the initial volume with different ethanol proportions. The reference wine (14.0% ethanol, 0.40 g/L volatile acidity) showed a bathochromic shift of 4 nm and a color enhancement (DeltaColor) of 41%, lower than that found for the reconstituted wine with the same ethanol content (53%). This discrepancy could be attributable to the loss of acetic acid during the ethanol elimination step. DeltaColor was 95% for the reconstituted wine without ethanol and decreased until 18% for the reconstituted wine with 22% ethanol. Copigmentation was important for reconstituted wines with ethanol contents typical for table red wine, showing DeltaColor between 53 and 57%. An increase in ethanol content in reconstituted wines was accompanied by an increase in the pH value. Perceivable changes in color (DeltaE > 1) followed every increase in ethanol content.

Noninvasive glucose monitoring by back diffusion via skin: chemical and physical enhancements.

Blood glucose levels are routinely obtained by invasive and painful methods using glucose meters and test strips. The development of less invasive or non invasive techniques would be beneficial for diabetes patients. In this study, a noninvasive method was evaluated using the back diffusion of glucose across skin with or without permeation enhancement methods. An in vitro model was utilized. The stratum corneum (SC) was the predominant barrier for both back and forward diffusion of glucose across skin. Surfactants with various charges and essential oils (cyclic monoterpenes) were used as chemical enhancers to promote the back diffusion of glucose. A cationic surfactant (benzalkonium chloride) showed the highest enhancement, followed by anionic and nonionic surfactants. d-Limonene and 1,8-cineole dispersed in appropriate proportions of ethanol could enhance the glucose diffusion after pretreatment of the skin surface. Electroporation, defined as a physical method, significantly increased the amount of glucose that diffused back. The percentages of diffused glucose by 300 V (volts) and 500 V high voltage pulses on skin for 10 min were found to be 45 and 75 times greater than the control group, respectively.

Effects of pregnancy and progesterone on the consumption of ethanol by the high ethanol preferring (HEP) rat.

A significant fraction of women continue to drink heavily during pregnancy, which is associated with the fetal alcohol syndrome, alcohol-related birth defects, alcohol-related neurodevelopmental disorder, and spontaneous abortion. The objective of this study was to determine whether the selectively bred genetic drinking Myers High Ethanol Preferring (HEP) rat would continue to drink through pregnancy. Rats from the F7 generation were screened by a 10-day 3-30% (v/v) ethanol concentration 'step up' procedure in order to determine the concentration which resulted in maximal drinking with an ethanol solution to total fluid ratio closest to 0.5. After baseline drinking of the preferred concentrations was established, female HEP rats were randomly selected for mating and their ethanol bottles were removed. Upon finding a 'sperm plug', male rats were removed and the ethanol was returned. A second group received injections of progesterone in sesame oil beginning with a 1.0 mg/kg/day dose which was increased to 3.0 mg/kg/day on gravid days (GD) 5-20. Vaginal smears confirmed that progesterone rendered the rats anoestrous. Neither pregnancy nor progesterone changed either the amount or proportion of ethanol consumed compared to the baseline period. The rats drank an average of 8.4 g/kg daily throughout pregnancy. A sharp drop in food intake was noted the day after mating. Beginning on GD 13, it was observed that pregnant rats showed a marked increase in the variance for proportion of ethanol consumed and body weight. Subsequently, only one of the eight impregnated rats successfully delivered a litter. The ethanol solution was removed and these rats mated again: seven of the eight rats delivered litters. These two findings suggest that the pregnant females must have begun to lose their litters on or after GD 13. Further, pregnancy does not affect the consumption of ethanol in the HEP rat. In addition, due to the fact that drinking by HEP rats during pregnancy leads to such a high rate of resorption of the fetus, this hybrid strain may also constitute a useful model for the study of alcohol-induced spontaneous abortion.

Stable carbon isotopic analysis and the botanical origin of ethanol in Brazilian brandies

Carbon isotopic composition (δ 13C) of Brazilian brandies was used to determine the contribution of sugar from C3 or C4 plants to their ethanol content. C3 plants have an average δ 13C value of −27‰, against an average value of −12‰ for C4 plants. This difference is large enough to permit determination of the origin of the ethanol fermented from plants. There are two types of brandy in Brazil: one called “conhaque-de-gengibre”, where ethanol from any plant can be used, and another called “brandy”, where only ethanol from grapes can be used. The less expensive brandies, classified as “conhaque de gengibre”, have their ethanol content derived exclusively from sugar-cane (average δ 13C equal to −12.9‰), while in the Brazilian brandies it was a mixture of sugar-cane and grapes (average δ 13C equal to −18.0‰). In Brazilian “brandies” there was an inverse relationship between its price and the carbon isotopic composition, indicating that higher prices is associated to larger proportions of ethanol from grapes.

Solvent extraction of pentachlorophenol from contaminated soils using water-ethanol mixtures

Pentachlorophenol (PCP) is a wood preserving agent that is commonly found in contaminated soils at wood treatment sites. The extraction of PCP from contaminated soils was evaluated using water-ethanol mixtures as solvents. A mixed solvent containing equal proportions of water and ethanol, a water-miscible mixture, proved effective in extracting PCP from both spiked and field contaminated soils. Maximum PCP recovery from soil occurred within the first hour of contact between soil and the mixed solvent. PCP extraction with the 50% water-ethanol mixture was comparable to extraction using Soxhlet and sonication procedures. In batch extraction experiments, 50% ethanol was effective in recovering PCP from soils spiked with up to 99 mg/kg PCP. This water-ethanol mixture was as effective as richer ethanol solutions in removing PCP from field soils found at a wood preserving site, extracting approximately 720 mg/kg PCP from one soil along with hydrocarbons (alkanes and PAHs) present in the field soil.

Transdermal delivery of sodium nonivamide acetate from volatile vehicles: effects of polymers

The permeation of sodium nonivamide acetate (SNA), a newly designed analogue of capsaicin, from ethanol/pH 4.2 buffer solutions containing antinucleant polymers across rat skin, was investigated. The in vitro release of SNA was determined under an open condition at 25°C and 65% relative humidity. Therefore, the influence of the evaporation of vehicle components on the permeation of SNA was examined. Evaporation of the vehicle led to so drastic compositional changes that supersaturation is attained quickly. However, supersaturated solutions started to crystallize reducing the thermodynamic activity of SNA. Antinucleant polymers were used in the preparation of volatile vehicles in order to maintain the increased activity state of the drug. Methyl cellulose (MC) and hydroxypropyl cellulose (HPC) were both the efficient antinucleant polymers to increase the permeation of SNA. The permeation of SNA determined from volatile vehicles with 2% MC showed the result that the flux of SNA reached maximum at a certain ethanol proportion. A part of ethanol in the vehicle may penetrate into the skin causing the dehydration of stratum corneum and, therefore, the reduction of SNA permeation. The permeation of SNA was increased when ethanol in the volatile vehicle was replaced by n-propanol which could be due to the increased SNA solubility and reduction of diffusional barrier of stratum corneum in the presence of n-propanol.

Genetics of Alcoholism: Rapid Development of a New High-Ethanol-Preferring (HEP) Strain of Female and Male Rats

A genetically based animal model of alcoholism has been developed in a relatively short period of 3 years. The new strain is characterized by an intense preference for ethanol over water as well as unique behavioral, neurochemical and other attributes. This new strain, termed high-ethanol-preferring (HEP) rats, was derived initially from selective cross-breeding of a variant strain of female Harlan Sprague–Dawley (SD) rats with the outbred Wistar line of male ethanol-preferring (P) rats. In this study, drinking patterns of both genders were obtained over 10 days by presenting water and ethanol in concentrations ranging from 3% to 30%. To expedite the development of the new strain, only three to five female and male rats served as breeders, which were chosen from all litters on the basis of their maximum g/kg intake integrated with proportion of ethanol to total fluid values. Profiles of intake of preferred concentrations of ethanol were obtained over 24 h of unlimited access as well as during 2-h intervals of limited access to ethanol. Levels of blood ethanol were measured in both female and male HEP animals during bouts of ethanol drinking in the limited access paradigm. By the sixth generation of HEP rats, ethanol consumption of the females often exceeded that of any other rat genetically bred to drink ethanol (e.g., at a concentration of 15.7%, 10.3 g/kg per day). Seven additional characteristics are notable: 1) the HEP rats prefer ethanol in the presence of a nutritious chocolate drink or nonnutrient sweetened solution (aspartame); 2) high levels of blood ethanol are associated with their drinking; 3) females drink significantly greater g/kg amounts of ethanol than HEP males and prefer a higher percent concentration of ethanol; 4) the drinking of ethanol by the female HEP animals does not fluctuate during the estrous cycle; 5) neurochemical assays show differential profiles of 5-HT, dopamine, and their metabolites in different regions of the brain; 6) measures of activity using the elevated plus maze, open field, and cork gnawing reveal differences between genders of HEP rats and SD rats; and 7) the HEP animals are without phenotypically expressed abnormalities. Finally, one cardinal principle derived from this study revealed that the breeding strategy to develop high-ethanol-drinking rats centers on the use of multiple solutions of ethanol whereby the intakes of ethanol in concentration of 9% through 20% dictate the ultimate selection of breeding pairs over successive F generations. Further, it is concluded that because of an intense rise in ethanol drinking of the F 1 generation of female HEP rats well above that of the parental SD female breeders, the complex genotypic characteristic of the male P rat is predominantly responsible for evoking ethanol drinking in female offspring.

Effects of Acetone, Ethanol, Isopropanol and Dimethyl Sulfoxide on Amylose-Iodine Complex†

The amylose-iodine (AI) complex formation was studied by absorption spectra in water and water-containing varying proportions of ethanol, acetone, isopropanol and dimethyl sulfoxide (DMSO). Complex formation is most favored in pure water and decreases as the proportion of nonaqueous solvent is increased. A decrease in the absorbance intensity at around 615 nm (for AI complex) is accompanied by a peak shift towards 550 nm and an increased absorbance at around 350 nm (for unbound iodine). The amount of the nonaqueous solvent added, as well as the order in which it is added relative to amylose and iodine solution; change remarkably the extent of the AI complex formation. A mechanism of the complex formation is proposed. † This paper was originally published in A35, 5. Due to a printing error, it is being reprinted here in its entirety.

Limited Access to Ethanol in Genetic Drinking Rats Is Suppressed While Feeding Is Enhanced by the Mixed 5-HT 1A Agonist/5-HT 2A Antagonist FG5938

Serotonin (5-HT) receptor agonists, antagonists, and mixed agonist/antagonists have been implicated in the volitional intake of ethanol in the rat and other species. The present experiments were undertaken to determine whether FG5938 (1-[4-( p-fluorophenyl)butyl]-4-(6-methyl-2-pyridinyl)-piperazine fumarate) would alter ethanol drinking in: genetic ethanol preferring (P) rats; and a new strain of high ethanol preferring (HEP) male and female rats derived from crossbreeding of P and a variant strain of Sprague–Dawley animals. After a preference test for solutions of 3 to 30% ethanol vs. water, each rat was given limited access to its maximally preferred concentration daily between 1600 and 1800 h; fluid intakes were recorded every 0.25 h. Once fluid consumption had stabilized over 4 days, saline vehicle, 2.5 mg/kg or 5.0 mg/kg FG5938 was injected subcutaneously 0.5 h prior to ethanol access on each of 3 consecutive days; thereafter, preference testing for ethanol continued for 4 additional days. Whereas the saline vehicle was without effect, FG5938 caused a fivefold decrease in total intake of ethanol from 1.7 to 0.3 g/kg and in proportion of ethanol to total fluid consumed from 0.42 to 0.03. The onset of the significant decline in ethanol drinking occurred during the latter 1.75-h interval. Further, both doses of FG5938, but not saline, increased the intake of food significantly. The decline in ethanol drinking was virtually identical in both P and HEP males and in female HEP rats. These results demonstrate that FG5938 affects ethanol drinking only after 0.5 h of its administration. Finally, it is envisaged that the ingestion of ethanol in genetic high drinking rats is mediated, in part, by central synapses utilizing both 5-HT 1A and 5-HT 2A receptors.

Effects of Acetone, Ethanol, Isopropanol, and Dimethyl Sulfoxide on Amylose-Iodine Complex

ABSTRACT The amylose-iodine (AI) complex formation was studied by absorption spectra in water and water containing varying proportions of ethanol, acetone, isopropanol and dimethyl sulfoxide (DMSO). Complex formation is most favored in pure water and decreases as the proportion of nonaqueous solvent is increased. A decrease in the absorbance intensity at around 615 nm (for AI complex) is accompanied by a peak shift towards 550 nm and an increased absorbance at around 350 nm (for unbound iodine). The amount of the nonaqueous solvent added, as well as the order in which it is added relative to amylose and iodine solution, change remarkably the extent of the AI complex formation. A mechanism of the complex formation is proposed.

Effect of Gasohol on The Rat Liver

Although there are a variety of gasoline ethanol mixtures proposed as neat fuels (ethanol 85% + gasoline 15% = E85; E95) for automobiles, gasohol (gasoline 90% + ethanol 10%) is presently used as a fuel in the United States. The adverse effects, if any, of gasohol ingestion are unknown; effects on the liver of rats administered gasohol are examined in this study.Twenty-four female Sprague-Dawley rats received daily, via gavage, one of the three concentrations of gasohol for 28 days; LD50/20, LD50/100 and LD50/1000, where LD50 = 1.5g ethanol / kg body weight (bw) and 14g gasoline / kg bw. The LD50 was based on that of gasoline, which was obtained from literature value.1 The amount of ethanol added to stock gasohol was only 1/10 its LD50, required to maintain the gasoline ethanol proportion of 9:1. Gasohol was administered in corn oil with total volume 10 ml. Animals that received only corn oil served as controls.

Female Syrian golden hamster: drinking of high concentrations of ethanol aversive to other mammals

The present experiments were designed to determine: 1) the pattern of preference for different concentrations of ethanol in the female Syrian golden hamster ( Mesocricetus auratus), and 2) the influence of drinking ethanol on their intakes of food and total calories. A standard three-bottle preference test was undertaken in six female hamsters over an 11-day period in which water was offered together with ethanol, which was increased in concentration over 11 clays from 3% to 50% as follows: 3%, 5%, 7%, 9%, 12%, 15%, 20%, 25%, 30%, 40%, 50%. Then, each hamster was offered its individually preferred concentration for a period of 8 days until the intake of ethanol had stabilized. During the preference testing for 3–25% solutions, the proportional intakes ranged between 0.6 and 0.8 whereas the mean absolute amount consumed per day increased from 2.3 to 16.1 g/kg at the 25% concentration. However, at the 50% concentration, ethanol drinking declined substantially to 8.7 g/kg per day. The overall mean percent concentration of ethanol preferred by the hamsters was 24.2 ± 1.5%. During the following 8-day period when the maximally preferred concentration of ethanol of each hamster was offered with water, the mean intake of ethanol was 17.9 ± 1.1 g/kg per day. Throughout the test sequence, the caloric intake of the animals was maintained in that calories obtained from food declined at the same rate as the calories obtained from ethanol in rising concentrations. These results reveal that the preference for ethanol of the female hamster is well above that reported in earlier studies in which preference was defined in terms of the proportion of ethanol to total fluid intake. Differences in procedure could account for these findings because the present experiments utilized single-animal housing, a triple bottle method, and measurement of g/kg per day obtained at 11 different concentrations of ethanol.

Relative Influence of Ethanol and Propylene Glycol Cosolvents on Deposition of Minoxidil into the Skin

Minoxidil, a potent antihypertensive, is moderately effective in the treatment of hair loss when it is applied to the scalp as a 2% solution in 60% ethanol, 20% propylene glycol and 20% water. Important questions remain concerning both the mechanism of delivery and the pathway of penetration of this drug from its ternary solvent system. Since preliminary studies in our laboratory indicated that water in the formulation influenced permeation far less than the other two solvents, we examined the relative deposition and penetration influences of binary combinations of ethanol and propylene glycol. When 50 μL/cm2of the formulations was spread over hairless mouse skin sections mounted in Franz diffusion cells, only small amounts of minoxidil were actually recovered from the receiver compartments. Nevertheless, more minoxidil penetrated the skin as the proportion of ethanol in the mixtures was increased. To determine if thesein vitroresults formed a representative picture of thein vivobehaviors of these vehicles, selected deposition experiments were performed on live, anesthetized mice under experimental conditions similar to those used in the diffusion cell work. The good agreement betweenin vivo andin vitrostudies may be a result of the relatively fast partitioning of the drug into the skin as compared to its diffusion through the skin.

ANAEROBIC TREATMENT OF DISTILLERY SLOPS IN THE CIRCUMSTANCES OF CENTRAL EUROPE

Anaerobic treatment of many kinds of slops is one of the most progressive ways for the reuse of this material. The special feature of Central Europe is that the largest proportion of ethanol is produced by fermentation, and the raw material in big distilleries is only sugar beet molasses. The consequence of this is a large production of slops in small regions, and as far as the quality of slops is concerned, a relatively high content of inert and nonbiodegradable organic compounds in comparison with other more valuable raw materials, such as grapes, fruits, cereals, potatoes, etc. A two-year operation of the pilot scale UASB reactor bas shown that molasses slops are a suitable material for anaerobic treatment The slops were diluted by other wastewaters from the distillery to a concentration of about 25 g.l‒1 COD and then treated in the pilot reactor at 32°C with the following average results: COD removal efficiency 78.8 %; volumetric loading rate 7.1 kg.m-3.d‒1; volumetric gas production 2.6 m3.m‒3.d‒1; specific gas production 0.47 m3.kg‒1. The results achieved confi11II that molasses slops are a source of energy. For example, Czech distilleries could potentially produce 12-17 million m3 of the valuable gas fuel per annum.

5-HT 2 receptor blockade by amperozide suppresses ethanol drinking in genetically preferring rats

Previously, it was shown that the unique diphenylbutylpiperazinecarboxamide derivative, amperozide (FG 5606), inhibits the volitional drinking of ethanol induced in the rat by the inhibitor of aldehyde dehydrogenase, cyanamide. In this study, the efficacy of this long-acting psychotropic agent and potent 5-hydroxytryptamine 2 (5-HT 2) receptor antagonist was examined in the genetic line of ethanol-preferring (P) and -nonpreferring (NP) rats. In both lines, the pattern of drinking of ethyl alcohol was determined by a standard preference test for 3–30% ethanol vs. water. Then, the maximally preferred concentration of ethanol was determined for each individual, which ranged from 9–15% for P rats and 9–13% for NP animals. After a 4-day predrug test, either the saline control vehicle or amperozide was administered SC b.i.d. at 1600 and 2200 h. The drug was given over a 3-day period in one of three doses: 0.5, 1.0, or 2.5 mg/kg. The intake of ethanol of P rats was reduced significantly in a dose-dependent manner in terms of both absolute g/kg and proportion of ethanol to water during injections of amperozide. The same doses of amperozide had no effect on the low intake of ethanol in NP rats. The saline control vehicle also did not alter the consumption of ethanol of P or NP rats. Further, neither the consumption of food nor level of body weight was affected by amperozide either during or after its administration. These results demonstrate that in the individual predisposed genetically to drink ethanol amperozide exerts a palliative effect on the aberrant preference for ethanol consumed in a pharmacologically significant amount. Presently, dopaminergic and serotonergic synapses in the brain are implicated in the genetic differences in the patterns of ethanol consumption that distinguish the P from the NP line of rats. Because amperozide influences the functional activity of both dopaminergic and serotonergic neurons in the mesolimbic system, it is envisaged that the drug attenuates ethanol drinking by way of its direct action on these neurons.