Suppression of acquisition of alcohol-drinking behavior by the concurrent availability of saccharin in Sardinian alcohol-preferring (sP) rats.

In the current study, we investigated the effect of the concurrent presentation of saccharin on the acquisition of alcohol-drinking behavior in selectively bred Sardinian alcohol-preferring (sP) rats. Alcohol-naive rats were given access to saccharin [0%, 0.01%, 0.1%, 1%, or 3% (weight/volume) in water], alcohol [10% (volume/volume) in water], and water under the home cage, three-bottle, free-choice regimen, with unlimited access for 24 h/day for 10 consecutive days. Intake of saccharin solution resulted as an inverted-U function of saccharin concentration, reaching polydipsic-like values at the 0.1% concentration. In contrast, alcohol intake was a U function of saccharin concentration, being virtually suppressed in the groups of rats exposed to the highly accepted 0.1% and 1% concentrations of saccharin. These results indicate that (1) the concurrent presentation of highly palatable solutions of saccharin suppresses acquisition of alcohol-drinking behavior in sP rats and (2) the suppressive effect of saccharin solutions on the acquisition of alcohol-drinking behavior in sP rats was positively related to their degree of acceptability. We hypothesize that an immediate and continuous access to the highly palatable saccharin solution may have distracted the rat, preventing it from consuming the amounts of alcohol solution needed to disclose and experience the psychopharmacologic effects of alcohol on which alcohol-drinking behavior in sP rats is based.     

The GABA(B) receptor agonists baclofen and CGP 44532 prevent acquisition of alcohol drinking behaviour in alcohol-preferring rats

AIMS: The present study investigated the effect of the gamma-aminobutyric acid (GABA)(B) receptor agonists, baclofen and CGP 44532, on the acquisition of alcohol drinking behaviour in selectively bred Sardinian alcohol-preferring (sP) rats. METHODS: Baclofen [0, 1 and 3 mg/kg, intraperitoneally (i.p.)] and CGP 44532 (0, 0.1, 0.3 and 1 mg/kg, i.p.) were administered immediately before alcohol presentation to alcohol-naive sP rats. Alcohol was offered under the two-bottle free-choice regimen with unlimited access for 24 h/day. Drug treatment was repeated once daily for 10 consecutive days. RESULTS: Baclofen and CGP 44532, dose-dependently and with comparable efficacy, suppressed alcohol intake; compensatory increases in water intake left total fluid intakes virtually unchanged. CONCLUSIONS: These results demonstrate that baclofen and CGP 44532 prevent the acquisition of alcohol drinking behaviour in sP rats, and suggest the involvement of the GABA(B) receptor in the mechanisms underlying the disclosure and experience of the reinforcing properties of alcohol in this rat line.     

Repeated exposure to alcoholic beer does not induce long-lasting changes in alcohol self-administration and intake in Sardinian alcohol-preferring and Sardinian non-preferring rats

AIMS: Rats avidly consume non-alcoholic beer, and addition of alcohol to non-alcoholic beer may function as a medium to induce intake of large amounts of alcohol in rats. The present study investigated whether Sardinian alcohol-preferring (sP) and Sardinian non-preferring (sNP) rats, initially exposed to non-alcoholic beer, and subsequently to non-alcoholic beer containing increasing concentrations of alcohol, would develop unusually high alcohol self-administration and drinking behaviours: (i) when alcohol was added to non-alcoholic beer, and (2) once beer was withdrawn and a plain alcohol solution was made available. METHODS: In Experiment 1, rats were exposed to operant, 30-min/day self-administration sessions of non-alcoholic beer with increasing concentrations of alcohol [0, 2.5, 5, 7.5, and 10% (v/v)] for a total of 45 days. After a brief 'beer-fading' phase, the rats were exposed to self-administration sessions of a plain 10% (v/v) alcohol solution. In Experiment 2, the rats were exposed to non-alcoholic beer with increasing concentrations of alcohol [0, 2.5, 5, 7.5, and 10% (v/v)] and water under the 2-bottle choice regimen with unlimited access (24 h/day) for a total of 35 days. After a brief 'beer-fading' phase, the rats were exposed to the choice between a plain 10% (v/v) alcohol solution and water. RESULTS: sP and sNP rats did not differ in self-administration (Experiment 1) and intake (Experiment 2) of non-alcoholic beer. In Experiment 1, as alcohol content increased, the amount of self-administered alcohol increased progressively in sP rats (up to 1-1.2 g/kg) and remained stable in sNP rats (approximately 0.65 g/kg). When the plain 10% alcohol solution was available, the amount of self-administered alcohol in sP rats initially dropped, and tended to increase-up to approximately 0.6 g/kg-on continuing exposure. In sNP rats, their lever-pressing behaviour was rapidly extinguished after beer withdrawal. In Experiment 2, as alcohol content was increased, daily alcohol intake increased progressively in sP rats (up to 8-9 g/kg) and averaged approximately 2.4 g/kg in sNP rats. When the plain alcohol solution was available, daily alcohol intake in sP rats was initially low, reaching control values on continuing exposure; conversely, daily alcohol intake was completely suppressed in sNP rats. CONCLUSIONS: These results suggest that exposure to alcoholic beer resulted in unusually high intakes of alcohol in both sP and sNP rats for as long as non-alcoholic beer was added to alcohol; however, these high levels of alcohol self-administration and intake were not maintained once non-alcoholic beer was withdrawn.     

High alcohol intake in female Sardinian alcohol-preferring rats

Sardinian alcohol-preferring (sP) rats have been selectively bred for high alcohol preference and consumption. When exposed to the standard, home cage 2-bottle “alcohol (10%, v/v) vs. water” choice regimen with continuous access, male sP rats consume daily approximately 6 g/kg alcohol. Conversely, when exposed to the intermittent (once every other day) access to 2 bottles containing alcohol (20%, v/v) and water, respectively, male sP rats display marked increases in daily alcohol intake and signs of alcohol intoxication and “behavioral” dependence. The present study was designed to assess alcohol intake in female sP rats exposed, under the 2-bottle choice regimen, to (a) 10% (v/v) alcohol with continuous access (CA10%), (b) 10% (v/v) alcohol with intermittent access (IA10%), (c) 20% (v/v) alcohol with continuous access (CA20%), and (d) 20% (v/v) alcohol with intermittent access (IA20%). Male sP rats (exposed to CA10% and IA20% conditions) were included for comparison. Over 20 daily drinking sessions, daily alcohol intake in female CA10% and IA20% rats averaged 7.0 and 9.6 g/kg, respectively. The rank of alcohol intake was IA20% > IA10% = CA20% > CA10%. Conversely, daily alcohol intake in male CA10% and IA20% rats averaged 6.0 and 8.2 g/kg, respectively. Comparison of female and male rats yielded the following rank of alcohol intake: female IA20% > male IA20% > female CA10% ≥ male CA10%. An additional experiment found that alcohol drinking during the first hour of the drinking session produced mean blood alcohol levels of 35–40 mg% and 85–100 mg% in the CA10% and IA20% rats, respectively. These results (a) extend to female sP rats previous data demonstrating the capacity of the IA20% condition to markedly escalate alcohol drinking, and (b) demonstrate that female sP rats consume more alcohol than male sP rats. This sex difference is more evident under the IA20% condition, suggesting that female sP rats are highly sensitive to the promoting effect of the IA20% condition on alcohol drinking. These data contribute to the characterization of sP rats as a model of excessive alcohol consumption.     

Saccharin consumption and the effect of a long-term exposure to a sweetened alcoholic solution in high- (UChB) and low- (UChA) alcohol-drinking rats.

An association between saccharin consumption and alcohol intake has been observed in rodent lines genetically developed for alcohol preference or alcohol avoidance. It has also been proposed that a sweetened alcohol solution can condition rats to consume high amounts of alcohol. This work had two aims. First, to study the relationship between saccharin and alcohol intake in both high-alcohol-drinking UChB rats and low-alcohol-drinking UChA rats and, second, to determine whether a long-term exposure to a sweetened alcohol solution can increase their voluntary alcohol consumption. For the first purpose, UChB and UChA rats were tested under a free-choice paradigm between two graduated bottles, one containing a saccharin solution (0.1, 0.2, or 0.4% [wt/vol]) and the other water. For the second purpose, UChB and UChA rats that were under free choice between 10% alcohol and water, were offered a 10% alcohol solution containing 0.2% saccharin, instead of 10% alcohol for 1 month and were then returned to free choice between 10% alcohol and water. The first experiment showed that both lines have a high preference for saccharin at any concentration, but UChB rats drank twice as much saccharin solution as UChA rats and consequently they increased significantly their total daily fluid intake. This fact has been suggested to be an animal analogue of the clinical phenomenon known as "loss of control." In the second experiment a long-term exposure to a 10% alcohol solution containing 0.2% saccharin induced a significant increase in alcohol consumption in UChB rats once saccharin was faded out, whereas the alcohol consumption in UChA rats returned to the previous low value. This result indicates that UChA rats have a genetic predisposition to avoid alcohol. In conclusion, the results reported here for UChB and UChA rats show an association between saccharin and alcohol preference, and suggest that their different genotypes are probably involved in alcohol aversion.     

Development of short-lasting alcohol deprivation effect in sardinian alcohol-preferring rats.

Alcohol deprivation effect (ADE), defined as a temporary increase in voluntary alcohol intake following a period of alcohol abstinence, was evaluated in selectively bred Sardinian alcohol-preferring (sP) rats. Alcohol was initially offered in free choice with water for 35 consecutive days (predeprivation phase). Subsequently, one group of rats was deprived of alcohol for 1, 3, 7, 15, 30, 90 or 180 consecutive days, while the second group had continuous access to alcohol (deprivation phase). Once alcohol was re-presented, alcohol intake in alcohol-deprived rats was recorded 1 and 24 h after alcohol re-presentation and compared to that monitored in alcohol-nondeprived rats over the same time periods (postdeprivation phase). Alcohol deprivation for 3 to 30 days resulted in a significant increase in voluntary alcohol intake only in the first hour of re-access. These results demonstrate the development of ADE in sP rats. However, the rapid return of alcohol intake to control levels is discussed as evidence in favor of a set-point mechanism capable of regulating alcohol-drinking behavior in sP rats.     

Differences in ethanol-induced conditioned taste aversion in Sardinian alcohol-preferring and Sardinian alcohol-nonpreferring rats.

In the present study, we investigated whether aversion to the pharmacological effects of ethanol developed to a differential extent in selectively bred Sardinian alcohol-preferring (sP) and Sardinian alcohol-nonpreferring (sNP) rats, and whether this different response was consistent with their genetically determined differences in ethanol preference and consumption. To this purpose, a conditioned taste aversion paradigm was used. Male sP and sNP rats were exposed to five sessions in which a 20-min availability of a saccharin solution (1 g/l) was paired to the injection of ethanol (0, 0.5, or 1 g/kg, i.p.), delivered immediately after removal of the saccharin bottle (conditioning phase). Subsequently, the choice between saccharin solution and water was offered for 18 consecutive daily 20-min sessions (postconditioning phase). Ethanol at 1g/kg produced a marked aversion to saccharin in sNP rats: The reduction in saccharin intake was already evident on the second day of the conditioning phase and lasted for 15 days of the postconditioning phase. In contrast, this dose of ethanol elicited a modest, if any, conditioned taste aversion in sP rats, although blood ethanol levels were comparable to those assessed in sNP rats. These results indicate the existence of a differential degree of aversion to the postingestional effects of ethanol between sP and sNP rats, and support the suggestion that it may contribute, at least in part, to the opposite preference for and consumption of ethanol monitored in these rat lines.     

Blood alcohol concentrations after scheduled access in high-alcohol-preferring mice.

Development of procedures yielding substantial blood alcohol concentrations during voluntary access to an alcohol solution in mice is necessary to further characterize genetic and neurobiologic mechanisms underlying alcohol self-administration. Although, in experimental situations, some populations of mice readily drink an alcohol solution, results from previous studies have not typically revealed high blood alcohol concentrations after voluntary access, probably because of the high alcohol metabolism rate in mice. Toward development of a murine drinking model, 36 selectively bred high-alcohol-preferring mice of both sexes were subjected to a 30-min scheduled-access procedure by using saccharin fading to gradually introduce an alcohol solution. Mice had ad libitum access to food and water 24 h a day. The alcohol solution was available 1 h after the start of the dark part of the cycle for 30 min per day, 5 days per week. After complete removal of saccharin from the drinking tubes, mice consistently drank 1.4 g/kg of a 10% [volume/volume (vol./vol.)] alcohol solution in 30 min. Analysis of tail blood samples, taken immediately after the end of the 30-min access period, indicated blood alcohol concentrations were tightly correlated with alcohol intakes (range, 6-130 mg/dl; average, nearly 60 mg/dl). A concentration-response function of 10%, 12%, 15%, 18%, and 21% (vol./vol.) alcohol solutions indicated an inverted U-shaped relation between alcohol intake and alcohol concentration, with peak intake of greater than 1.75 g/kg per 30 min when a 15% alcohol solution was available. No sex differences were seen. These findings indicate the utility of this procedure in obtaining pharmacologically relevant blood alcohol concentrations after voluntary oral self-administration of an alcohol solution in mice.     

Binge drinking in alcohol-preferring sP rats at the end of the nocturnal period

Sardinian alcohol-preferring (sP) rats have been selectively bred for high alcohol preference and consumption using the standard 2-bottle “alcohol (10%, v/v) vs. water” choice regimen with unlimited access; under this regimen, sP rats daily consume 6–7 g/kg alcohol. The present study assessed a new paradigm of alcohol intake in which sP rats were exposed to the 4-bottle “alcohol (10%, 20%, and 30%, v/v) vs. water” choice regimen during one of the 12 h of the dark phase of the daily light/dark cycle; the time of alcohol exposure was changed daily in a semi-random order and was unpredictable to rats. Alcohol intake was highly positively correlated with the time of the drinking session and averaged approximately 2 g/kg when the drinking session occurred during the 12th hour of the dark phase. Alcohol drinking during the 12th hour of the dark phase resulted in (a) blood alcohol levels averaging approximately 100 mg% and (b) severe signs of alcohol intoxication (e.g., impaired performance at a Rota-Rod task). The results of a series of additional experiments indicate that (a) both singular aspects of this paradigm (i.e., unpredictability of alcohol exposure and concurrent availability of multiple alcohol concentrations) contributed to this high alcohol intake, (b) alcohol intake followed a circadian rhythm, as it decreased progressively over the first 3 h of the light phase and then maintained constant levels until the beginning of the dark phase, and (c) sensitivity to time schedule was specific to alcohol, as it did not generalize to a highly palatable chocolate-flavored beverage. These results demonstrate that unpredictable, limited access to multiple alcohol concentrations may result in exceptionally high intakes of alcohol in sP rats, modeling – to some extent – human binge drinking. A progressively increasing emotional “distress” associated to rats' expectation of alcohol might be the neurobehavioral basis of this drinking behavior.     

The relationship between saccharin and alcohol intake in rats.

Male rats were given daily sessions during which a palatable saccharin solution was available. Based on intakes averaged over 3 days, groups with low, intermediate, or high intake of saccharin were formed. These rats were then given daily sessions in which alcohol (2-8%) or water were available. Initially, sessions were conducted with rats on a food restriction schedule; in later sessions, food was available ad lib. When rats were food restricted, there were no differences among the groups in terms of alcohol or water intake. When the food restriction schedule was discontinued, alcohol intake in the intermediate and high saccharin intake groups was generally higher than that of the low saccharin group. On the final series of alcohol sessions, the high saccharin group consumed significantly more 2% and 6% alcohol than the low saccharin group. These results are consistent with reports which have found that rats selected for high or low alcohol intake have corresponding high and low intakes of saccharin.     

Autoshaping of ethanol drinking in rats: effects of ethanol concentration and trial spacing.

In two studies, we evaluated the effects of ethanol concentration and trial spacing on Pavlovian autoshaping of ethanol drinking in rats. In these studies, the brief insertion of an ethanol sipper conditioned stimulus (CS) was followed by the response-independent presentation of food unconditioned stimulus (US), inducing sipper CS-directed drinking conditioned responses (CRs) in all rats. In Experiment 1, the ethanol concentration in the sipper CS [0%-16% volume/volume (vol./vol.), in increments of 1%] was systematically increased within subjects across autoshaping sessions. Groups of rats received sipper CS-food US pairings (Paired/Ethanol), a CS-US random procedure (Random/Ethanol), or water sipper CS paired with food US (Paired/Water). In Experiment 2, saccharin-fading procedures were used to initiate, in the Ethanol group, drinking of 6% (vol./vol.) ethanol in 0.1% saccharin or, in the Water group, drinking of tap water in 0.1% saccharin. After elimination of saccharin, and across days, the duration of access to the sipper CS during each autoshaping trial was increased (5, 10, 12.5, 15, 17.5, and 20 s), and subsequently, across days, the duration of the mean intertrial interval (ITI) was increased (60, 90, 120, and 150 s). In Experiment 1, Paired/Ethanol and Random/Ethanol groups showed higher intake of ethanol, in terms of grams per kilogram of body weight, at higher ethanol concentrations, with more ethanol intake recorded in the Paired/Ethanol group. In Experiment 2, the Ethanol group drank more than was consumed by the Water group, and, for both groups, fluid intake increased with longer ITIs. Results support the suggestion that autoshaping contributes to sipper CS-directed ethanol drinking.     

The α2-adrenergic receptor agonist,clonidine, reduces alcohol drinking in alcohol-preferring (P) rats

Evidence suggests that noradrenergic signaling may play a role in mediating alcohol-drinking behavior in both rodents and humans. We have investigated this possibility by administering clonidine to alcohol-drinking rats selectively bred for alcohol preference (P line). Clonidine is an α₂-adrenergic receptor agonist which, at low doses, inhibits noradrenergic signaling by decreasing norepinephrine release from presynaptic noradrenergic neurons. Adult male P rats were given 24 h access to food and water and scheduled access to a 15% (v/v) alcohol solution for 2 h daily. Rats received intra-peritoneal (IP) injections with clonidine (0, 10, 20, 40, or 80 μg/kg body weight [BW], 10–11 rats/treatment group) once/day at 30 min prior to onset of the daily 2 h alcohol access period for 2 consecutive days. Clonidine, in doses of 40 or 80 μg/kg BW, significantly reduced alcohol intake on both days of treatment (p < 0.001). Two weeks later, rats were treated with clonidine for 5 consecutive days and clonidine, in doses of 40 or 80 μg/kg BW, reduced alcohol intake on all 5 treatment days (p < 0.001). Clonidine did not alter water consumption during the daily 2 h free-choice between alcohol and water. In a separate group of male P rats, clonidine (40 μg/kg BW) suppressed intake of a saccharin solution (0.04 g/L). These results are consistent with and complement our previous findings that the α₁-adrenergic receptor antagonist, prazosin, decreases voluntary alcohol drinking in alcohol-preferring rats, but suggests that effects of clonidine may not be specific for alcohol. The results suggest that although activation of the noradrenergic system plays an important role in mediating voluntary alcohol drinking, care is needed in selecting which drugs to use to suppress central noradrenergic signaling in order to maximize the selectivity of the drugs for treating alcohol-use disorders.     

Reduction of alcohol intake by the positive allosteric modulator of the GABAB receptor, rac-BHFF,in alcohol-preferring rats

Previous research has demonstrated that treatment with the positive allosteric modulator (PAM) of the GABA_B receptor (GABA_B PAM), rac-BHFF, suppressed lever-responding for alcohol and amount of self-administered alcohol in Sardinian alcohol-preferring (sP) rats. The present study was designed to extend the investigation on the anti-alcohol effects of rac-BHFF to alcohol drinking behavior. To this end, sP rats were exposed to the homecage, 2-bottle “alcohol (10%, v/v) vs water” choice regimen, with unlimited access for 24 h/day. rac-BHFF was administered once daily and for 7 consecutive days at the doses of 0, 50, 100, and 200 mg/kg (i.g.). Treatment with rac-BHFF resulted in an immediate, stable, and dose-related reduction in daily alcohol intake; the overall magnitude of reduction in alcohol intake averaged approximately 25%, 40%, and 65% in 50, 100, and 200 mg/kg rac-BHFF-treated rat groups, respectively. An increase in daily water intake fully compensated the reduction in alcohol intake, so that daily total fluid intake was unaffected by treatment with rac-BHFF. Daily food intake tended to be reduced only by the highest dose of rac-BHFF. These results complement closely with previous data indicating that (a) rac-BHFF suppressed operant, oral alcohol self-administration in sP rats and (b) the prototypic GABA_B PAMs, CGP7930 and GS39783, reduced alcohol drinking in sP rats. However, while the reducing effect of CGP7930 and GS39783 on the daily alcohol intake tended to vanish after the first 2–3 days of treatment, the reducing effect of rac-BHFF on daily alcohol intake remained unchanged over the entire 7-day treatment period. These data strengthen the hypothesis that GABA_B PAMs may represent a step forward in the search for GABA_B receptor ligands with therapeutic potential for alcoholism.     

Development of alcohol deprivation effect in rats: lack of correlation with saccharin drinking and locomotor activity.

The present study addressed the relationship between the parameters of saccharin drinking behaviour and locomotor activity in an open field environment and long-term alcohol self-administration. In a 22-day initiation phase, male Wistar rats were presented with increasing concentrations of ethanol (2-8%, v/v) in a choice with water. The rats were then given the choice between water and two ethanol solutions (8 and 16%). Every 28 days, ethanol was withdrawn for 5 days. The ethanol intake and the transient increase in ethanol consumption after each of six deprivation episodes (alcohol deprivation effect) was monitored and correlated with parameters of the subsequent saccharin drinking and open field tests. The total ethanol intake (g/kg/24 h) as well as the consumption of 16% ethanol were stable over time. However, the magnitude of the alcohol deprivation effect increased with the repeated deprivation episodes. None of the parameters measured in the open field or the saccharin drinking tests correlated with either ethanol consumption or the alcohol deprivation effect. These results suggest that (1) repeated episodes of ethanol deprivation may increase the magnitude of the alcohol deprivation effect, (2) neither saccharin drinking nor locomotor activity correlates with long-term ethanol drinking behaviour in rats.     

Stable preference for high ethanol concentrations after ethanol deprivation in Sardinian alcohol-preferring (sP) rats.

Results of a recent study have demonstrated that exposure to multiple ethanol concentrations and repeated ethanol deprivation periods in Indiana ethanol-preferring (P) rats resulted in the development of an alcohol deprivation effect (ADE; the temporary increase in voluntary ethanol intake after a period of deprivation from ethanol) characterized by consumption of intoxicating amounts of ethanol. The current study was designed to possibly extend these results to Sardinian alcohol-preferring (sP) rats, generated with the same selective program previously used for P rats. To this aim, ethanol-naive sP rats were exposed initially to the home cage four-bottle choice [10%, 20%, and 30% (vol./vol.) ethanol solutions and water] for eight consecutive weeks. Subsequently, rats were divided into two groups: The first group had continuous access to the four-bottle regimen (nondeprived rats), and the second group was exposed to five cycles of 14-day periods of deprivation from ethanol and 14-day periods of reexposure to the four-bottle regimen. An ADE developed after each deprivation period. However, the extra intake of ethanol was limited to the first hour of each reaccess period. Magnitude of ADE did not change with repeated periods of deprivation. However, a shift in preference toward the two highest concentrations of ethanol solutions was evident from the first reexposure to ethanol and was maintained throughout the study. These results provide further evidence on the heterogeneity of ethanol-drinking behavior among rat lines selectively bred for high ethanol preference and consumption.     

Taste-aversion-prone (TAP) rats and taste-aversion-resistant (TAR) rats differ in ethanol self-administration, but not in ethanol clearance or general consumption.

Taste-aversion (TA)-prone (TAP) rats and TA-resistant (TAR) rats have been developed by means of bidirectional selective breeding on the basis of their behavioral responses to a TA conditioning paradigm. The TA conditioning involved the pairing of an emetic-class agent (cyclophosphamide) with a novel saccharin solution as the conditioned stimulus. Despite the absence of ethanol in the selective breeding process, these rat lines differ widely in ethanol self-administration. In the current study, blood alcohol concentrations (BACs) were determined after 9 days of limited (2 h per day) access to a simultaneous, two-bottle choice of a 10% ethanol in water solution [volume/volume (vol./vol.)] or plain water. The BACs correlated highly with ethanol intake among TAR rats, but an insufficient number of TAP rats yielded measurable BACs to make the same comparison within this rat line. The same rats were subsequently exposed to 24-h access of a two-bottle choice (10% ethanol or plain water) for 8 days. Ethanol consumption during the 24-h access period correlated highly with that seen during limited access. Subsequent TA conditioning with these rats yielded line-typical differences in saccharin preferences. In a separate group of rats, ethanol clearance was determined by measuring BACs at 1, 4, and 7 h after injection of a 2.5-g/kg dose of ethanol. Ethanol clearance was not different between the two lines. Furthermore, the lines did not differ with respect to food and water consumption. Therefore, the TAP rat-TAR rat differences in ethanol consumption cannot be attributed to line differences in ethanol metabolism or in general consummatory behavior. The findings support our contention that the line differences in ethanol consumption are mediated by differences in TA-related mechanisms. The findings are discussed with respect to genetically based differences in the subjective experience of ethanol.     

Experimentally induced glucose intolerance increases oral ethanol intake in rats

A number of studies have shown a relationship between glucose tolerance and ethanol intake. The present study uses a relatively simple procedure to induce glucose intolerance to test whether this condition is sufficient to produce an increase in chronic ethanol intake in male rats. Subjects were divided equally into four groups where they were given access to one of four solutions: peppermint-flavored sucrose (40%), peppermint-flavored saccharin (0.1%), peppermint in water (0.1%), or water alone presented three times a week, for a period of 11 weeks. After 12 weeks all animals were subjected to an oral glucose tolerance test which revealed that the chronically prepared sucrose animals had become glucose intolerant. At the start of week 13 all animals were given access to a 6% ethanol solution flavored with peppermint in place of the previous solutions for a period of 11 weeks. Sucrose animals displayed an immediate preference for ethanol and consumed approximately three times more ethanol than the remaining groups. The results of this study indicate that rats that are made glucose intolerant by long term access to a high concentration of sucrose, when given the opportunity, will subsequently choose to drink more ethanol than control animals.     

Examination of the negative alcohol-deprivation effect in the golden hamster (Mesocricetus auratus).

When ethanol-consuming animals are denied access to their ethanol solution for a period of days, there is typically a temporary but substantial increase in their ethanol consumption when the solution is returned. Golden hamsters are unusual in that they actually decrease their consumption of a 7% ethanol solution (v/v) under these circumstances. There experiments were therefore undertaken to further investigate this unusual negative alcohol-deprivation effect (ADE) in hamsters. In Experiment 1, the negative ADE was observed across a wide range of ethanol concentrations; adult male hamsters were given access to food, water, and either a 7.5, 15, or 30% (v/v) ethanol solution, and when the ethanol solution was withdrawn for seven days and then returned, ethanol consumption decreased significantly for several days and then recovered. Experiment 2 demonstrated that similar negative deprivation effects occur with glucose (15% w/v) and saccharin (0.1%) solutions, suggesting that the nutritional and pharmacological properties of ethanol do not play an important role in the negative ADE of hamsters. In Experiment 3, when hamsters with continuous access to either an ethanol, glucose, or saccharin solution were switched to an alternate-days access schedule, their intake of solutions decreased substantially, supporting the conclusion that a common mechanism accounts for the golden hamster's negative deprivation responses to ethanol solutions and to other solutions, both nutritive and nonnutritive. Hypotheses relating to the mechanism underlying negative deprivation effects are presented and discussed.     

Initial acceptance of ethanol: gustatory factors and patterns of alcohol drinking

Individual differences related to taste, determined by prior two-bottle tests of quinine and saccharin selection against water, were found to be related to the initial selection of 15% ethanol solution during the first week of access by 60 randomly bred male rats. The 36 rats that drank the least alcohol during the first week (mean +/- SE: 0.49 +/- 0.06 g/kg/day), however, greatly increased their intake during the second and third weeks, to the level of the 24 initially high alcohol drinkers (4.07 +/- 0.39 g/kg/day during 1st week), and the influence of gustatory factors was no longer apparent. Subsequently, the initially low rats drank less alcohol when saccharin was the alternative fluid. The results can be interpreted as showing that initially low rats, that only drank rather large amounts of alcohol after prolonged exposure, resemble Cloninger's Type 1 alcoholics not only in this temporal pattern but also in being high in novelty seeking, and low in harm avoidance and reward dependence, and that the initially high rats that spontaneously drank rather large amounts even in the first week show the opposite characteristics and resemble Type 2 alcoholics. Although these rats are not themselves models for alcoholism, the results nevertheless suggest it might be possible to develop two separate animal models for the two types of alcoholism.     

Conditioned taste aversion and the Myers' high-ethanol-preferring rat

AIMS: Male and female Myers' high-ethanol-preferring (mHEP) rats were compared to outbred controls in a taste aversion paradigm. METHODS: Alcohol-na?ve rats were adapted to a 2-h access to water. Each rat was given either 0.05% saccharin (w/v) or 7% ethanol (v/v) as a novel solution for 1 h, after which either 0.5 M LiCl, as the aversive stimulus, or NaCl, as the control, was injected intraperitoneally. Each rat was tested 48 h later by presentation of the same solution. RESULTS: After LiCl injections, saccharin consumption declined 21.6% in female Sprague-Dawley, 9.5% in female mHEP, 33.3% in male Wistar, and 38.3% in male mHEP rats. Ethanol consumption in these groups declined by 88.5, 30, 45 and 52%, respectively. These mHEP rats were then screened for 24-h alcohol consumption on a 10-day 3-30% ethanol vs water 'step-up' procedure. During the step-up procedure, only the male mHEP rats trained with ethanol for taste aversion drank less ethanol at the 3-5% concentrations than did rats trained with saccharin. The female mHEP rats did not learn an aversion to either saccharin or ethanol. CONCLUSIONS: The female mHEP rat consumes copious amounts of ethanol, but the basis for this consumption may be different from that of the male mHEP rat.