Charles E. Denning

Initiation of ethanol self-administration in the rat using sucrose substitution in a sipper-tube procedure

Abstract Rationale: The concepts of appetitive and consummatory behaviors provide a framework for examining ethanol-drinking behavior. However, traditional studies of ethanol self-administration using dipper procedures make separating the appetitive from the consummatory components difficult. Objective: This study compared the ability to initiate ethanol self-administration using a new sipper-tube self-administration procedure with the older established sucrose-substitution initiation model that employed dipper presented reinforcement. The new model was developed to allow for an assessment of the appetitive and consummatory components in ethanol self-administration. Methods: For the sipper-tube procedure, the rats were initiated to self-administer ethanol using a sucrose-substitution procedure that provided limited access to a sipper tube containing ethanol. This procedure required the completion of a fixed ratio requirement (FR4) in order to gain access to a sipper tube for 20 min. Initially, a 20% sucrose solution with no ethanol was provided in the sipper tube. Over sessions, the concentration of sucrose was reduced and the ethanol concentration increased, until 10% ethanol in water was the solution presented. A second group of animals was initiated to self-administer ethanol using the dipper-presentation procedure employed in our laboratory for many years. This group was used for comparison of the effectiveness of initiation in the sipper-tube procedure. Results: Following initiation, the sipper-tube rats self-administered 10% ethanol in water with intakes averaging 0.75 g/kg during the 20-min drinking period. Increasing the ethanol concentrations as high as 20%, increased intakes as high as 1.5 g/kg. The ethanol intakes observed were similar to those obtained with the dipper initiation procedure but occurred in one-third of the time. Conclusions: The sipper-tube procedure employed here results in similar ethanol self-administration behavior as has been found with a dipper presentation procedure. More importantly, however, it allows for a separation of the appetitive and consummatory components of ethanol self-administration. This separation may prove useful for examining the strength of ethanol-seeking behaviors without the confound of increasing levels of ethanol interacting with the appetitive seeking behaviors.

Effects of the Atypical Antipsychotic Remoxipride on Alcohol Self-Administration

Remoxipride is a dopamine (DA) D2 antagonist that produces fewer of the side effects normally associated with chronic DA antagonist administration. It has been demonstrated that DA antagonists can reduce the desire for a second drink in alcoholics. However, because of the usual side effects associated with DA antagonist administration, chronic use as an adjunct to alcoholism treatment has not been considered. Because the DA D2 antagonist haloperidol reduces ethanol self-administration in an operant animal model of ethanol self-administration, this study was designed to determine whether remoxipride would produce similar results. Six Long-Evans rats were initiated to self-administer ethanol in daily 30-min operant sessions using a sucrose-substitution procedure. Following establishment of ethanol-reinforced lever pressing, remoxipride (0.5, 1.0, 5.0, or 10.0 mg/kg) or haloperidol (0.01, 0.05, or 0.1 mg/kg) were injected 30 min prior to the sessions. Remoxipride produced an approximate 50% reduction in the number of ethanol presentations per session at the highest dose tested (10.0 mg/kg) and did so by terminating the ethanol-drinking bout earlier in the session. Haloperidol also decreased ethanol presentations with the highest dose tested (0.1 mg/kg) producing the largest effect. These data indicate that remoxipride produces reductions in ethanol-reinforced responding similar to those observed with another DA antagonist. Because remoxipride produces fewer of the side effects commonly observed with chronic DA antagonist administration, it could prove to be a useful adjunct in the treatment of excessive alcohol consumption.

Chronic Ethanol Self-Administration in a Continuous-Access Operant Situation: The Use of a Sucrose/Ethanol Solution to Increase Daily Ethanol Intake

The addition of sucrose to an ethanol solution increases both limited- and continuous-access ethanol consumption. The present study examined if the increased intakes in a continuous-access condition could produce withdrawal signs indicating physical dependence on ethanol. Rats were maintained in a continuous-access operant situation in which one lever press on one lever resulted in the presentation of a food pellet, whereas one lever press on a second lever presented 0.1 ml of fluid in a dipper. Water was available from a drinking spout. Ten rats received a 10% sucrose/20% ethanol mixture in the dipper and six rats 10% sucrose. After 30 days the animals were tested for withdrawal signs after 8 h without ethanol using an activity test and response to key shaking. They were then given an additional 30 days of access to the solutions and retested for withdrawal. This was followed by a final 30 days of access and a third withdrawal test. Over the 90 days, the sucrose/ethanol group consumed 8-10 g of ethanol per kilogram of body weight per day. Over this time both groups gained weight. At the third withdrawal test, a significant reduction in activity occurred in the ethanol-drinking group, compared with the sucrose group. No severe withdrawal effects were observed to the key shake test. The results suggest that the higher ethanol intakes previously observed using this sucrose/ethanol solution can be maintained over long periods of time. Although this intake was not sufficient to produce severe withdrawal signs, the results suggest that longer exposure might result in more severe ethanol dependence.

Effects of Sucrose-Substitution Initiation on Patterns of Drinking by Lewis Rats During Continuous Alcohol Access

Initiation of alcohol drinking using the sucrose-substitution procedure was studied in inbred Lewis rats. One group of animals was initiated to self-administer alcohol prior to being placed in the continuous-access condition, whereas the second group of animals did not undergo initiation. During the continuous-access period, the animals were housed in operant chambers where they had continuous access to alcohol (10% v/v), food, and water during daily 23-h experimental sessions. After 5 weeks of baseline conditions, the response, requirement for food was increased over weeks. This was followed by weekly increases in the ethanol response requirement with the food response requirement returned to baseline conditions. In the continuous-access condition, both groups consumed similar amounts of alcohol by the end of the 4-week baseline period and showed similar numbers of dippers presented per alcohol bout and number of alcohol bouts per day. During the food response requirement manipulation, alcohol consumption increased for both groups but intake increased significantly more for the noninitiated group. The difference between groups was accounted for by a larger number of alcohol drinking bouts per day for the noninitiated group. Alcohol consumption decreased at each increase in ethanol reinforcement response requirement for both groups. Alcohol-reinforced responding per session increased for the noninitiated animals but remained unchanged for the initiated group during this condition. Responding increased substantially for both groups when the alcohol reinforcement response requirement was returned to baseline conditions. These results suggest that alcohol may serve more as a food source for noninitiated animals during the food reinforcement manipulation and that initiation may result in more resistance to change during the alcohol reinforcement manipulation. These data show that the type of initial exposure to alcohol can impact future drinking patterns.

The use of nonalcoholic beer as the vehicle for ethanol consumption in rats

Adult, male rats were presented in their home cages with either a nonalcoholic beer, the nonalcoholic beer with 10% ethanol added, or a choice between the two fluids. Although alcohol intake was increased by using the beer vehicle when alcohol was presented as the only available fluid, total daily consumption was not found greater than previous studies using other tastants to mask the alcohol taste. When given a choice, the rats preferred the nonalcohol-containing nonalcoholic beer to the alcohol-containing nonalcohol beer. After prolonged ethanol exposure in the home cage using the nonalcoholic beer vehicle, a subgroup of rats was tested in an operant paradigm to determine if ethanol presentation would maintain lever press behavior. There was little indication that, after this home cage procedure, ethanol functioned as an effective reinforcer. Therefore, although it appears that the use of nonalcoholic beer as the vehicle for making alcohol solutions can increase alcohol consumption, the utility of the nonalcoholic beer is no better than that of adding sweeteners.

Effects of prior ethanol exposure on ethanol self-administration in a continuous access situation using retractable drinking tubes.

To examine whether exposure to ethanol influences subsequent ethanol consumption using a continuous access procedure, two groups of rats were given differing initial exposure to ethanol. One group underwent a sucrose-substitution initiation procedure. The second group received abbreviated initiation consisting of one-session exposure to each ethanol/sucrose combination used in standard initiation. The animals were then provided with 23 h/day access to ethanol (10%, v/v) from a retractable drinking tube. Food pellets were available following a single-lever press, and water was available from a sipper tube. After 5 weeks, the data indicated that few significant differences existed between the groups on total ethanol (g/kg), food or water consumed. The overall intake (g/kg/day), number of ethanol bouts per day, and amount consumed per bout (g/kg/bout) were substantially lower than observed in previous research using ethanol presented in a dipper. However, differences in g/kg per ethanol bout did differ significantly between the two groups with the group receiving standard initiation showing more ethanol consumed per bout. These data agree with our previous work indicating that initiation results in larger drinking bouts.