Ethanol intake as a function of concentration during food deprivation and satiation

Ethanol intake and responding of 6 male albino rats were measured at concentrations of 0 (water control) 2, 4, 8, 16, and 32% (W/V) during daily 1-hr sessions in operant conditioning chambers. The rats were run first food deprived (80% of free-feeding weight) and then food satiated (free access to food in home cages). Ethanol intake was greater when the rats were food deprived, but under both food conditions: (1) ethanol intake exceeded that of water at all concentrations, (2) quantity (mg) consumed increased with the concentration, and (3) the highest rate of responding occured at the beginning of the session. In a second experiment, fixed-ratio responding maintained by contingent presentation of 32% (W/V) ethanol exceeded water control responding. This finding strengthened the conclusion that this concentration can serve as a reinforcer for the food-satiated rat.     

Ethanol drinking by rhesus monkeys as a function of concentration

Ethanol deliveries maintained fixed-ratio (FR) responding of three rhesus monkeys during daily 3-h sessions. At FR values of 8 or 16, ethanol concentration was varied in the sequence 0 (water), 8, 11.3, 16, 22.6, 32, 8, and 0% (w/v). As the ethanol concentration increased, number of liquid deliveries decreased, although intake of ethanol (g/kg/session) increased somewhat. Blood ethanol levels were usually greater than 200 mg% and occasionally greater than 300 mg%.These data were reported to the Committee on Problems of Drug Dependence (1976) and were part of a doctoral dissertation by J. E. Henningfield     

Establishment and maintenance of oral ethanol self-administration in the baboon

A simple and reliable method was developed to study the self-administration of orally available ethanol by baboons. Two baboons were individually housed in a minimally controlled laboratory environment with visual and auditory access to other baboons and to laboratory technicians. The cages were equipped with standard drinking bottles and spouts. Each baboon was fed his entire daily ration of dry food at the same time each morning, at which time a fresh solution was added to the liquid reservoir. Three hours later, the amount of liquid consumed was measured. This procedure generated high rates of water drinking during the 3-h sessions (“food-induced drinking”). Next, the water available during the sessions was replaced by gradually increasing concentrations of aqueous ethanol (0.5–8%, w/v). When 8% ethanol was reached, the concentration was held constant across daily sessions as session feedings were gradually reduced and shifted to 30 min postsession. Eventually, daily test sessions consisted of simply 3 h access to ethanol, and water was continuously available during the 21-h intersession period. Over a range of ethanol concentrations of 8–32%, ethanol intake (g/kg) and blood ethanol levels remained fairly constant, while volumes (ml) of solution consumed were inversely related to the concentration. Finally, an additional liquid spout was added to each cage and the baboons were provided concurrent access to both ethanol (8%) and water during the sessions. The results indicated clearly that ethanol had come to serve as a positive reinforcer for both of these baboons. This simple preparation should be particularly useful in laboratories that are not equipped with the elaborate technology required in earlier described preparations, and might lend itself to the study of orally effective drugs other than ethanol.     

Ethanol-reinforced responding and intake as a function of volume per reinforcement.

Number of ethanol reinforcements obtained and ethanol intake (mg/100 g body weight/hr) of 3 food-deprived rats were measured over a range of dipper volumes during daily 1 hr sessions. The rats had free access to water in their home cages between sessions. Ethanol concentration was 8 percent (W/V); each response was reinforced. As the volume per reinforcement increased, ethanol intake tended to increase while the number of reinforcements obtained decreased systematically. Responding was maintained by 8 percent (W/V) ethanol but not by water.     

Ethanol intake in the absence of concurrent food reinforcement

Schedule-induced polydipsia (SIP) occurred in four rats placed on concurrent food (1 min VI) and water (CRF) reinforcement schedules. During extinction (i.e. absence) of concurrent food reinforcement either water or an ethanol concentration of 2, 4, 8, 16, or 32% (w/v) was present. Measurements of water and ethanol intake were made before and after substituting these ethanol concentrations for water during SIP. After ethanol experience during SIP, the ethanol volume consumed and ethanol reinforcements obtained were significantly greater than water control values. Thus, ethanol served as a reinforcer. At ethanol concentrations of 32% (w/v) through 2% (w/v), volumes consumed exceeded water control values. Following ethanol experience during SIP, ethanol volume intake and reinforcements significantly increased. However, the magnitude of the increase was not significant when the initial values, i.e., those obtained prior to ethanol experience, were significantly greater than water control values. The quantity of ethanol intake increased directly with the concentration, and the highest rate of intake occurred during the first half hour ethanol was available.This research was supported in part by Research Grants MH-15349 and MH-14112 from the United States Public Health Service to the University of Minnesota. We thank Dr. Glenn E. Bartsch for his advice concerning the statistical analysis of the data.U.S.P.H.S. Postdoctoral Research Fellow 1 FO 2 MH 467700-1.     

Rapid establishment of ethanol as a reinforcer for rats

Daily 6-h sessions were run during which each lever press by rats produced brief access to water, or to 8?/0 (W/V) ethanol on experimental days. Food pellets were presented noncontingently on a 1 min fixed-time schedule during the last, 4 h of each session. A stable baseline of water responding developed, characterized by little or no responding during the first 2 h followed by high rates and schedule-induced polydipsic drinking during the last 4 h. Following the development of a stable water baseline, 8% (W/V) ethanol was substituted for water on alternate days. After one previous session with ethanol, rats' responding for ethanol during the first 2 h of a session substantially exceed water baseline rates, indicating that ethanol had been established as a reinforcer. Subsequently, when food pellet presentations were discontinued, and the ethanol concentration was increased from 8 to 16 to 32% (W/V), ethanol intake persisted at values exceeding water control levels; these results confirm that ethanol was functioning as a reinforcer.     

Ethanol reinforced behavior assessed with a concurrent schedule

Oral ethanol (5% v/v) reinforced responding was studied in three rats using a concurrent fixed ratio (FR) schedule with water available at second lever. First, concurrent (FR8 FR8) responding on both levers for water presentation was established. Then a concurrent (FR8 FR8) water-ethanol presentation schedule was introduced and a food ration was placed in the chamber at the beginning of the session. Within 12 sessions, ethanol responding developed and within-session feeding was discontinued. When stable concurrent water-ethanol performance was achieved, average ethanol responding was 11 times greater than water responding, even when ethanol availability switched from one lever to the other. During the one hour session, in some cases, sufficient ethanol was ingested to produce blood ethanol levels between 30 and 50 mg/100 ml. As the ethanol FR requirement was increased for four sessions each to FR10, 12, 14, 16, 18, 20, 40 and 50, rats continued to respond for ethanol, and in some rats, ethanol preference was maintained even when the ethanol FR was 50 while the water FR remained at 8.     

Effects of removing food on maintenance of drinking initiated by pairings of sipper and food

Two experiments evaluated the effects of removing food presentations on the maintenance of drinking induced by experience with sipper — food pairings. In Exp 1, ethanol drinking was induced in non-deprived Long-Evans rats by Pavlovian conditioning procedures employing an ethanol sipper as conditioned stimulus (CS) and food pellet as unconditioned stimulus (US). The Paired/Ethanol group received presentations of the ethanol sipper CS followed immediately by the response-independent presentation of the food pellet US. The Random/Ethanol group received the ethanol sipper CS and food US randomly with respect to one another. For both groups, the concentration of ethanol in the sipper CS [(3%, 4%, 6%, 8% (vol./vol.)] was increased across sessions, and, as in previous studies employing low concentrations of ethanol in non-deprived rats (i.e., maintained with free access to food in their home cages), the two procedures induced comparable levels of sipper CS-directed ethanol drinking. Removing food US presentations had no effect on sipper CS-directed ethanol drinking in either group. In Exp 2, groups of non-deprived Long-Evans rats were trained either with water or ethanol in the sipper CS paired with food US. Removing food US presentations had no effect on ethanol drinking in the Paired/Ethanol group, but water drinking in the Paired/Water group declined systematically across sessions. Results indicate that food US presentations contribute to the maintenance of water drinking but not to the maintenance of ethanol drinking. Implications for accounts of ethanol drinking based on Pavlovian sign-tracking, behavioral economics and intermittent sipper procedures are considered.     

Ethanol as a reinforcer for rats: Effects of concurrent access to water and alternate positions of water and ethanol

Water and ethanol solutions were concurrently made available on a continuous reinforcement schedule to 4 food-deprived male albino rats during daily 1-hr sessions in an operant conditioning chamber equipped with 2 levers and 2 liquid dippers. The number of ethanol reinforcements substantially exceeded the number of water reinforcements for each rat at each concentration studied (8, 16, and 32% w/v). Water reinforcements were low in number and did not vary with ethanol concentration. As the ethanol concentration was increased, the number of ethanol reinforcements obtained decreased, while the quantity consumed (mg/100 g of body weight/hr) increased. The highest rate of responding occurred at the beginning of the session.     

Ethanol as a reinforcer: Effects of fixed-ratio size and food deprivation

Rats having prior experience with ethanol drinking were subjected to geometrically increasing fixed-ratio (FR) schedules of ethanol reinforcement (8% W/V). The rats were tested first food deprived and then food satiated. Each third day ethanol was the reinforcer (0.25 ml/reinforcement), while on other days water, which served as the vehicle control, was available. Food satiating the rats decreased responding for ethanol whereas responding for water was not changed. Under both food conditions ethanol maintained responding at FR's up to 256 with response totals exceeding water control values. As the FR size increased to intermediate values, the number of ethanol responses increased. Further FR increases resulted in decreases in ethanol responding. The pattern of FR responding was similar to that maintained by other reinforcers. Maximum ethanol responding occurred at the beginning of the 6-h sessions, followed by a pause and then intermittent bursts of responding. Water responding was not characterized by a specific pattern. It was inferred that the odor of ethanol functioned as a discriminative stimulus, and it was concluded that ethanol served as a reinforcer for the rat.This research was supported in part by U.S.P.H.S. grant MH 20919-01 to the University of Minnesota. Portions of these data were presented at the Fall Meeting of the American Society for Pharmacology and Experimental Therapeutics, August, 1969, in Pittsburg, Pennsylvania; at the Tenth Annual Meeting of the Psychonomic Society, November, 1969, St. Louis, Missouri; and at the Thirty-second Meeting of the Committee on Problems of Drug Dependence, National Academy of Sciences—National Research Council, February, 1970, in Washington, D.C.U.S.P.H.S. Postdoctoral Research Fellow 1 FO 2 MH 46770-01.     

Reinforcer interactions under concurrent schedules of food,water, and intravenous morphine

Responding by six rats was maintained under a concurrent chained fixed-ratio 1, fixed-ratio 9 schedule (conc chain FR1 FR9) of food, water, and morphine presentations. The subjects had continuous access to the schedule contingencies on a reversed 12-h light-dark cycle. Local rates and temporal patterns were very similar for responding maintained by the three reinforcers with food and water intake occurring predominantly during the dark cycle, while morphine infusions were evenly distributed. Food and water extinction (24-h duration) decreased the number of ratios completed on both the food and water levers. Moreover, food extinction resulted in a large increase in I.V. morphine self-administration. Morphine extinction increased responding on the morphine lever while almost eliminating responding on the water lever. Changes in the dose of morphine (2.5–40 mg/kg/injection) did not significantly affect food and water intake, but were inversely related to responding on the morphine lever. Saline substitutions resulted in effects similar to those observed during morphine extinction. The schedule used in this study provides a method for examining the specificity of a number of pharmacological and neurochemical manipulations.     

Effects of feeding regimen on ethanol intake by guinea pigs

During daily two-hr sessions, guinea pigs licked a drinking tube filled with either 0 (tap water), 2, 4 or 8% (v/v) ethanol solution under three feeding regimens. Consumption of each solution was highest when sufficient food to maintain subjects at 90% of free-feeding weight was provided during sessions, lower when the same food ration was provided after sessions, and lowest when ad lib access to food was provided within and between sessions. However, this decrease in consumption across feeding regimens was inversely related to ethanol concentration. Under all feeding regimens, volume of solution consumed decreased with increasing ethanol concentration while milligrams ethanol consumed increased with ethanol concentration. These results are similar in some respects to previous findings with rats and monkeys, suggesting that further studies of oral ethanol self-administration by guinea pigs may be merited.     

Ethanol drinking by rhesus monkeys with concurrent access to water.

Three monkeys were provided concurrent access to water and ethanol in concentrations of either 8, 16 or 32% (w/v) during daily 3-hr sessions. The monkeys were those for whom ethanol had been established as a reinforcer in an earlier study in which only ethanol or water was available. Ethanol was preferred to water at all concentrations and volume of ethanol consumed was inversely related to ethanol concentration. Quantity of ethanol (g/kg of body wt.) consumed remained relatively constant, and blood ethanol determinations confirmed that the monkeys were drinking ethanol. Water drinking occurred at negligible levels except by one monkey at 16 and 32% who followed ethanol drinking bouts by water bouts (chasers) in a manner similar to that reported in other studies. Two monkeys were also provided concurrent access to 8% ethanol and water during 23-hr daily sessions. Under these conditions, ethanol was consumed every few hours to the near exclusion of water. The significance of this study lies largely in its procedure; that is, the development and application of a concurrent water-ethanol preparation in which ethanol serves as a reinforcer for rhesus monkeys. This preparation should be useful in the evaluation of a wide range of factors suspected to control alcoholic drinking.     

Resumption of ethanol-seeking behaviour in rats

Reexposure to alcohol may induce subjective craving and relapse to drug self-administration in ex-alcoholics. In this study, we proposed a rat model of "first-drink"-induced drug-seeking relapse. Responding was established in Long Evans rats under a fixed-ratio [FR5:S(1)] schedule for oral ethanol. Substitution of water for ethanol solution resulted in extinction of the self-administration. When responding for 8% ethanol and ethanol intake were stable for at least three consecutive 30min sessions, ethanol delivery was discontinued and only three water dipper cup presentations were available upon responding (3[FR5:water]). When the number of active lever presses decreased to a low stable level, responding was considered extinguished. In Experiment 1, subjects under "extinction" were challenged with three 8% ethanol dipper cup presentations. The re-exposure to ethanol was able to significantly reinstate responding in all subjects. Latency to complete the ethanol presentation significantly decreased compared to the value observed during the previous "extinction" session. In Experiment 2, other subjects were tested for extinction and then reexposed to 4, 8 or 16% ethanol. All three concentrations significantly increased active lever presses, but with different patterns of responding. The resumption of responding was linearly correlated to the ethanol concentration but no significant dose-effect relationship was found. In Experiment 3, reexposure to 8% ethanol in nondeprived rats induced a resumption of responding not significantly different from the effect observed in a restricted diet condition. These results demonstrate that ethanol reexposure is able to reinstate ethanol-seeking behaviour in rats with a past history of ethanol self-administration, and that this effect does not depend on a food motivation drive related to the calorific value of ethanol.     

Attenuation of ethanol intake by contingent punishment of food-maintained responding

Two food-deprived rats responded under a concurrent fixed-ratio 12 (food) fixed-ratio 1 (8% ethanol) reinforcement schedule in which a tone occurred during every second or every fourth interpellet interval. When ethanol-maintained lever presses during the presence of the tone shifted the food schedule to one in which electric shock punishment occurred, ethanol-maintained responding consistently decreased. The decrease in the frequency of ethanol-maintained responding varied directly with shock voltage from 25 to 100 V, and occurred during intervals with the tone present and absent. These results indicate that ethanol in take may be attenuated by contingent changes in a concurrent food schedule.     

Establishment of etonitazene as a reinforcer for rats by use of schedule-induced drinking

Drinking of etonitazene HCl by 6 rats was studied during daily 4-hr sessions. Five related experiments were conducted sequentially. In the first experiment schedule-induced polydipsia was established. Subsequently, etonitazene concentrations (1.25, 2.5 and 5.0 μg/ml) were substituted for water, and intake of large quantities of the drug occurred. In the second experiment the concurrent food reinforcement schedule was discontinued and lever presses maintained by etonitazene (5 μg/ml) persisted. In the third experiment the number of lever presses required per dipper presentation of etonitazene (5 μ/ml) was increased, and rate of lever pressing increased directly with the response requirement whereas number of dipper presentations remained constant. In the fourth experiment water was substituted for the 5 μg/ml etonitazene solution. Water responding declined to low rates, but when etonitazene was reintroduced, responding increased to previous levels. Thus, etonitazene (5 μg/ml) was functioning as a positive reinforcer. In the final experiment, progressive increases in the etonitazene concentration (5, 10, 20 and 40 μg/ml) resulted in both systematic decreases in response rate and increases in quantity (μg) consumed.     

Etonitazene as a reinforcer: Oral intake of etonitazene by rhesus monkeys

Drinking of etonitazene HCl was studied in three rhesus monkeys during daily 3-h sessions. As the drug concentration was increased, the number of liquid deliveries decreased, and etonitazene intake (g/kg body weight) increased. As fixed-ratio (FR) requirements were increased, rate of responding increased, and liquid deliveries slightly decreased. When water was substituted for the drug, there was a large increase in responding for several sessions, followed by a slow decline to low rates. When etonitazene was reintroduced, responding abruptly increased to previous drug levels. These data suggest that etonitazene can serve as a positive reinforcer when taken orally by rhesus monkeys.     

The effects of feeding conditions on drug-reinforced behavior: Maintenance at reduced body weight versus availability of food

Recent research has shown that food deprivation increases drug self-administration in rats and rhesus monkeys. The purpose of the present study was to examine two variables related to this food-deprivation effect: maintenance of rats at reduced body weights and the absence of food. Etonitazene HCl was established as a reinforcer orally for 12 rats according to procedures previously used in experiments reported by this laboratory. Lever-pressing behavior was maintained under fixed-ratio (FR) schedules during daily 1-h sessions by etonitazene or water, which were available either concurrently or on alternating days. In the first experiment, six rats were maintained at 75% of their free-feeding weights. The effect of presenting the daily food allotment at 23, 4, 2, 1, or 0 h before their daily drug or water self-administration session was studied. When the rats were fed 23, 4, or 2 h before the session, etonitazene dipper presentations were at maximum levels and were substantially higher than for water. When the rats were fed during (0) or 1 h before the session, the number of etonitazene dipper presentations was lower, but it exceeded those for water. Under conditions of complete food satiation (0 h deprived-100% body weight), etonitazene and water dipper presentations were both low, and there were no differences between them. In the second experiment, six rats maintained at 75% of their free-feeding weights were trained to respond for etonitazene or water on alternating days. When they were subsequently food satiated (100% body weight), drug- and water-maintained behavior decreased to low levels. These rats were then deprived of food for 4 or 16 h before their daily 1-h session, and responding did not increase. Body weight did not decrease below 100%. These results suggest that maintenance at reduced body weight rather than the absence of food is the determinant of increased rates of drug-reinforced behavior.     

Determinants of increased drug self-administration due to food deprivation

Changes in oral etonitazene self-administration were compared in four groups of rats that were maintained at 100, 95, 85, or 75% of their pre-experimental free-feeding body weights. Etonitazene (5 g/ml) or water was available for 16 h according to a fixed-ratio (FR) 1 schedule. Each liquid delivery (0.1 ml) was contingent upon a lever-press response. During food deprivation etonitazene intake gradually increased to over two-fold as body weights decreased over 25 sessions; etonitazene intake was inversely proportional to body weight. The 75% weight group showed stereotypy, self-mutilation and large variability in daily etonitazene intake. In another experiment a range of deprivation conditions was studied in a group of six rats with etonitazene (5 g/ml) or water available on an FR 8 schedule during 1-h sessions. When the rats were gradually food satiated, etonitazene-maintained behavior declined but remained higher than water-maintained behavior; however, when they were abruptly food satiated, etonitazene-maintained behavior decreased to low levels.     

Ethanol intakes and preferences in the desalivate rat

Desalivate and control rats were tested for ethanol versus water preference (5%, 10% and 20% (v/v) ethanol solutions). Each concentration of ethanol was presented for six days in an ascending, descending, or mixed presentation schedule. Following preference tests, intakes of first 10% (15 days), then 5% (15 days), and finally 10% (5 days) ethanol as the only available fluid were determined. Blood ethanol concentrations were measured (22:00 hr, 24:00 hr, 02:00 hr) during the final 10% ethanol intake test. Desalivate and control rats showed similar aversions to ethanol at all concentrations with relative ethanol intake being a negative function of concentration. During ethanol and water intake tests, desalivates drank significantly greater amounts (ml/100 g body weight) of all drinking fluids than controls. However, for both groups intake of 10% ethanol was reduced significantly from water baseline levels. Although desalivates consumed as much ethanol as controls, their blood ethanol concentrations at all times tested were slightly lower than controls. During the ethanol intake test desalivate rats lost body weight, while control rats gained body weight.