Forrest J. Files

Effects of continuous versus limited access to ethanol on ethanol self-administration

Eight male, experimentally naive Long-Evans rats were housed in operant chambers 23 h per day following initiation to self-administer ethanol. While housed in the chambers, the animals had continuous access to food pellets according to a fixed ratio 1 schedule of reinforcement, 10% ethanol (v/v) according to a fixed ratio 4 schedule of reinforcement and water in a drinking tube with licks recorded via a drinkometer. Over a series of experimental phases, daily availability of the ethanol solution was limited to 16, 6, 4, 2, or 1 30-min period per day. The 1 30-min period access was examined during the 12th hour or the second hour of the daily sessions. Over the course of the experiment, total responses on the lever that operated the dipper, g/kg per day and number of ethanol drinking bouts per day decreased significantly as the number of daily access periods decreased. On the other hand, the number of dippers presented per ethanol bout, g/kg per ethanol bout and ethanol bout duration increased, with significant increases in dippers per bout occurring when one 30-min access period per day was provided. These data indicate that the size of a single ethanol drinking bout can be increased somewhat by limiting the opportunity to obtain ethanol reinforcement and agrees with earlier research that has shown similar effects.

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.

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.

Behavioral Pharmacology of Alcohol

The actions of ethyl alcohol (ethanol) on behavior are diverse and depend on amount of ethanol administered, the time-course of administration, route of administration, and particularly blood ethanol level. Blood ethanol level is determined by the administration parameters, exposure history (both long term and recent), and environmental context. A wide spectrum of behavioral effects have been studied, particularly positive reinforcing actions maintaining self-administration and aversive effects observed in conditioned taste aversion. This chapter reviews the behavior pharmacology of ethanol.