Oral ethanol self-administration in rats: models of alcohol-seeking behavior.

While various methods have been used to initiate ethanol drinking in animals, the development of models in which animals will perform some specific behavior in order to obtain the opportunity to drink ethanol has been fraught with difficulty. In the past several years, new procedures have been developed in which rats, neither food nor fluid deprived, will perform an operant task reinforced by the presentation of ethanol. This paper reviews some of these recent findings and presents new data concerning these models of oral ethanol self-administration as measured in an operant paradigm.

Relation of ethanol self-administration to feeding and drinking in a nonrestricted access situation in rats initiated to self-administer ethanol using the sucrose-fading technique.

Free-feeding male Long-Evans rats (N = 8) were initiated to self-administer 10% ethanol using a sucrose-fading procedure. Following initiation, they were placed into chambers which allowed for the continuous monitoring of feeding, water drinking and ethanol self-administration. All rats continued to daily self-administer ethanol in the continuous access situation. Ethanol drinking at certain times during the day appeared to be related to feeding bouts (prandial drinking). However, at other times, nonprandial ethanol self-administration occurred. These nonprandial ethanol drinking episodes, while not at levels of excessive ethanol intakes, were at levels well above water intake when water was substituted for ethanol. These findings suggest that ethanol intake in continuous access conditions is not solely a function of feeding behavior and that following initiation, ethanol-seeking behavior was maintained in a continuous access situation.

Haloperidol and apomorphine effects on ethanol reinforcement in free feeding rats.

Free feeding male Long Evans rats were trained to lever press on a Fixed Ratio 8 schedule for 10% ethanol reinforcement. Mean ethanol intake in 30-minute sessions was 0.38 g/kg. Subcutaneous apomorphine (APO: 0.025 to 0.5 mg/kg) and haloperidol (HAL: 0.005 to 0.0625 mg/kg) administered 15 minutes before sessions dose-dependently reduced responding, but only APO reduced momentary response rates. Low doses of HAL reduced the effect of 0.3 but not 0.05 mg/kg APO. When the rats were food-restricted, control response rates decreased, and APO (0.025 and 0.05 mg/kg) had no further effect. Results were discussed in terms of dopamine involvement in the mechanism of ethanol reinforcement.

Oral ethanol reinforcement in the rat: effect of the partial inverse benzodiazepine agonist RO15-4513.

The partial inverse benzodiazepine agonist RO15-4513 has been found to reverse the sedating and anti-conflict effects of acute ethanol administration. In non-food or fluid-deprived rats, orally self-administering 10% ethanol in an operant situation, RO15-4513 resulted in a dose-dependent suppression on ethanol intake. Doses of 0.3, 1.0 and 3.0 mg/kg suppressed responding from approximately 25% to 60% respectively. A dose of 0.1 mg/kg had no significant effect upon responding. These findings were discussed in terms of the potential independence of brain mechanisms related to ethanol reinforcement and sedation.

Initiation of ethanol-maintained responding using a schedule-induction procedure in free feeding rats.

A schedule-induced adjunctive drinking procedure was used to initiate ethanol self-administration in free feeding rats. The rats were first trained on a FI 90-sec schedule with 20% sucrose reinforcement, and then ethanol was made concurrently available on a CRF schedule on a second lever. After 25 concurrent sessions, the sucrose was removed and the ethanol response requirement was brought to FR8. Finally, ethanol concentrations were varied up to 40%. Of 11 rats, 8 responded for sucrose on the FI 90 sec schedule, and 5 of those responded for 40% ethanol at FR8. These results were compared to previous studies using the same procedure in food-restricted rats and other procedures in free feeding rats. Possible explanations for the lower success using schedule induction in nondeprived rats were discussed.

Effect of pimozide on home cage ethanol drinking in the rat: dependence on drinking session length.

A stimulus-fading procedure was used to initiate ethanol drinking in free-feeding Long Evans rats. During daily half-hour drinking sessions in the home cage, a combination of sucrose and ethanol was first presented to the rats; gradually the sucrose concentration was reduced and the ethanol concentration increased until after 7 weeks the rats were drinking 10% ethanol with no sucrose. After stabilization of intake, either pimozide (PIM, 0.25, 0.50 and 1.00 mg/kg) was injected 4 h before drinking sessions or (d)-amphetamine (DEX, 0.25 and 0.50 mg/kg) was injected 15 min before sessions. The 0.50 and 1.00 mg/kg PIM doses and the 0.50 DEX dose significantly reduced intake compared to vehicle injections. In the second part of the experiment, the rats were given 24-h access to 10% ethanol and water in a two-bottle choice procedure. In this condition, 0.50 mg/kg PIM failed to reduce intake compared to vehicle. The critical difference between the two procedures seems to be that with the 30-min sessions, PIM injections were timed to have their maximal effect during testing. With 24-h sessions, decreases in intake produced by PIM could have been compensated for by increases after the drug had worn off. The hypothesis that dopamine is necessary for ethanol reinforcement receives support from the PIM effect on the 30-min sessions. The DEX effect extends the generality of our previous finding that DEX reduces ethanol-reinforced lever pressing in free-feeding rats.

Oral ethanol reinforcement in the rat: effects of acute amphetamine.

Six male Long Evans rats, reduced to 80% body weight by food restriction, were trained to lever press using 5% ethanol and water reinforcement on a concurrent FR8 FR8 schedule. After responding had stabilized, d-amphetamine (0.25 mg/kg, 0.50 mg/kg, and 1.00 mg/kg) or drug vehicle was injected 15 minutes before the 30-minute sessions. In comparison with the vehicle injections, the 0.25 mg/kg amphetamine dose was followed by a nonsignificant trend towards increased ethanol responding, the 0.50 mg/kg dose produced no trend, and the 1.00 mg/kg dose significantly decreased ethanol responding. These effects resemble those of amphetamine on food responding by food-deprived rats. Since both ethanol and amphetamine act upon brain catecholamine systems, possible involvement of catecholamines in reinforcement and arousal was discussed in relation to these results.

Oral ethanol reinforcement: interactive effects of amphetamine, pimozide and food-restriction.

Twelve male Long Evans rats, trained to lever press using 10% (v/v) oral ethanol reinforcement, were maintained with ad lib access to food and water in the home cage. After stabilization of responding, the rats were randomly divided into two groups: Group P received pimozide (PIM) injections (0.1 to 0.5 mg/kg) and Group A received d-amphetamine (DEX) injections (0.05 to 0.5 mg/kg). Following the sequence of either PIM or Dex injections, all rats were given four different combinations of PIM + DEX injections. The lower doses of amphetamine did not affect responding, but 0.5 mg/kg significantly reduced responding. All PIM doses except the lowest reduced responding. The combined PIM + DEX doses all reduced responding, in some cases further than either constituent dose alone. Next, all rats were reduced to 80% of their free feeding weights by food restriction, and tested with 0.25 mg/kg DEX, 0.1 mg/kg PIM, and 0.1 PIM + 0.25 DEX. As a result of food restriction, baseline responding increased significantly. The 0.25 mg/kg DEX dose tended to increase responding even above this baseline increase, while both PIM and PIM + DEX reduced responding.