Schedule-induced ethanol polydipsia: enhancement by saccharin.
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Alcohol Drinking↗
Biomedical subjects
H H Samson
Publications and source records attributed to H H Samson.
Oral self administration of ethanol in free feeding rats.
The use of animal models to study factors involved in excessive alcohol intake has prompted a number of investigators to propose criteria for an optimal model. One of these criterion, oral ingestion of intoxicating amounts of ethanol without concomitant weight loss and/or food restriction, has proven difficult to fulfill, especially when using rats. The following study reports a conditioning paradigm which was used to establish oral ethanol self administration in free feeding rats. Through initial reinforcement of 5% (v/v) ethanol consumption with 20% (w/v) sucrose solution, rats were trained to work for and consume concentrations of ethanol up to and including 40%. Blood ethanol levels above 100 mg ethanol/dl blood were frequently found. A control group, induced to drink quinine with the same procedures, indicated the relative importance of ethanol's pharmacological effect in maintaining high levels of self administration. The results show ethanol can maintain oral self administration of intoxicating quantities of high ethanol concentrations in free feeding rats, when its initial consumption is paired with an additional reinforcer.
Administration, Oral↗
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.
Animals↗
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.
Alcohol Drinking↗
Ethanol preference following the sucrose-fading initiation procedure.
Lever responding maintained with ethanol reinforcement at concentrations up to 20% (v/v) was initiated in non-food and -water deprived rats via a sucrose-fading procedure. Home cage two-bottle preference tests between water and 10% ethanol were conducted before (pre) and after (post) the ethanol initiation procedure to determine the effect of initial ethanol preference on ethanol initiation and of initiation on later ethanol preference. Initial preference testing found that the rats could be divided into two groups, animals with low ethanol preference scores (preference below 25%) and those with moderate ethanol preference scores (preference between 25% and 50%). All animals were successfully initiated with the sucrose-fading procedure to lever press with ethanol reinforcement. Following initiation, home cage preference was markedly increased for the initially low-preferring rats (from 12% to 43%), while moderate-preferring rats showed only slight increases (from 37% to 47%). The shift in ethanol preference was discussed in terms of the relation between ethanol preference and behavioral history.
Alcohol Drinking↗
Oral ethanol self-administration in a continuous access situation: relation to food response requirements.
Rats (N = 8) were housed (23 hr/day) in a test chamber in which the presentation of food pellets and 10% ethanol were a function of a concurrent fixed-ratio schedule of reinforcement. Water was available from a drinking tube. Following a 90-day period with food pellets presented on a fixed-ratio one schedule (FR 1) and ethanol on a FR 4, the FR schedule for food presentation was systematically increased. Daily food intake declined as the FR increased up to FR 64. Decreases in food were accompanied by reduced water consumption and a three-fold increase in ethanol intake. The major increase in ethanol intake was accounted for by an increase in the number of ethanol bouts/day rather than an increase in bout size. The 24-hr cyclic pattern of food, water and ethanol ingestive behaviors found in the 90-day FR 1 period was maintained as the food presentation schedule increased. Food, ethanol, and water intake returned to the pre-FR-manipulation levels with the introduction of the food FR 1 condition. The results were discussed in terms of caloric, fluid, and activity changes resultant from the effects of the FR manipulation. No single factor could account for the increased ethanol consumption. These effects were related to previous work which demonstrates increased ethanol intake when response parameters of concurrent reinforcements are changed.
Alcohol Drinking↗
Oral ethanol self-administration: a behavioral pharmacological approach to CNS control mechanisms.
Using rats which are self-administering ethanol in an operant situation, we have tested a variety of agonists and antagonists in an attempt to determine the role various CNS neurotransmitters may play in ethanol drinking. The major emphasis of the work has been on the dopaminergic and the benzodiazepinergic systems. This paper reviews prior work and provides new data on additional agonists and antagonists. The data suggest a possible reciprocal interaction between dopamine and benzodiazepine brain systems. This hypothesis is based on the change in pattern of lever responding which results when various agonists, antagonists and inverse agonists related to these neurotransmitters are compared. That is, similar changes in response pattern are found for dopamine agonists and benzodiazepine inverse agonists. On the other hand, dopamine antagonists and benzodiazepine agonists are similar to each other and produce a different set of changes. A neural circuit for a reciprocal interaction between the ventral tegmentum and the nucleus accumbens is proposed as one possible pathway which may be involved in these observations.
Alcohol Drinking↗
Ethanol self-administration in a nonrestricted access situation: effect of ethanol initiation.
Two groups of rats (male, Long-Evans) were studied in a continuous access situation, in which ethanol, food and water intake patterns were monitored, 23 h/day. One group of rats was initiated to lever press for ethanol prior to study in the continuous access situation by use of a secondary-conditioning procedure. The other group had no prior initiation. It was found that the ethanol self-administration pattern of the initiated rats was similar to a previous study using another initiation procedure. After four weeks, the noninitiated group also demonstrated an ethanol intake pattern similar to initiated animals. However, the specific nature of individual ethanol drinking bouts in the noninitiated animals was found to be different, suggesting that initiation resulted in larger and more ethanol-drinking bouts. In addition, the noninitiated animals failed to show any home-cage shift in ethanol preference, which is observed after the use of the initiation procedures. The only major difference found between the sucrose-substitution initiation procedure and the secondary-conditioning procedure occurred when response requirements to obtain food were increased. In this situation, ethanol intake increased only in the sucrose-substitution initiated animals. The relation of this finding to the underlying theoretical basis for each type of initiation procedure is discussed.
Animals↗
Ethanol drinking patterns in a continuous-access operant situation: effects of ethanol concentration and response requirements.
Rats, initiated to self-administer ethanol with either a sucrose-substitution procedure or a secondary-conditioning procedure, were maintained in a continuous-access environmental system in which operant lever press responses were required to receive 10% ethanol and food reinforcement. Water available from a drinking tube was electronically monitored to detect licks. Total daily consumption and patterns of food, water, and ethanol responding were analyzed under conditions in which the concentration of ethanol presented as a reinforcer was either 10% or 20%, and the response requirement for ethanol reinforcement was either a fixed ratio 4 schedule or a fixed ratio 1 schedule. Either increasing the ethanol concentration or decreasing the response requirement resulted in an increase in total daily ethanol intake. There was no significant difference between initiation procedures. These results are similar to observations in studies using a limited-access operant situation. This increased ethanol intake resulted from a complex alteration in the daily ethanol drinking pattern. The greatest ethanol intakes were observed when both the ethanol concentration was increased and response requirement was decreased. This was predominantly the result of increasing the number of ethanol drinking bouts per day when the response requirement was decreased, and by decreasing individual bout size by less than half when the ethanol concentration was doubled. These studies indicate that concentration of the ethanol presented as the reinforcer and the response cost required for reinforcement are involved in regulating ethanol consumption in the continuous-access condition. Type of initiation did not appear to interact with these variables.
Alcohol Drinking↗
Effects of morphine on acquisition and maintenance of ethanol and water intake patterns in rats.
Two experiments were conducted to assess the effects of chronic subcutaneous injections of morphine (1.0 mg/kg) or saline on the pattern and amount of sweetened ethanol and water intake in fluid restricted Long-Evans rats. Following daily injections, 2-h two-bottle choice tests were conducted with water and an ethanol solution (15% ethanol v/v in 5% sucrose w/v). During a 20-day acquisition phase (Experiment 1), ethanol intake patterns and amounts did not differ between saline (n = 6) and morphine (n = 6) groups. Both groups exhibited ethanol intake patterns that decreased exponentially throughout the session suggesting control by fluid restriction procedures. Morphine decreased water intake during initial periods of each session and increased intake during later periods. In Experiment 2, morphine and saline injections were reversed across three phases with the same rats. Morphine increased total ethanol consumption during the first few days of each 15-day phase, but the groups did not differ thereafter, and the initial increases produced no statistically significant group differences. Additionally, morphine augmented ethanol intake in early portions of sessions, while water intake was decreased and increased during early and later portions of each session, respectively. Analysis of the data from the last 5 days of each phase indicated that, when injected with morphine, the group which received saline during acquisition consumed significantly more ethanol solution than the group injected with morphine during acquisition. The effect on patterns of water and ethanol intake were observed, regardless of the drug injected during acquisition.(ABSTRACT TRUNCATED AT 250 WORDS)
Alcohol Drinking↗
Specific decreases in ethanol- but not water-reinforced responding produced by the 5-HT3 antagonist ICS 205-930.
The serotonin 5-HT3 antagonist ICS 205-930 has been shown to block the discriminative stimulus properties of ethanol and decrease voluntary intake, suggesting a possible role for 5-HT3 systems in the reinforcing effects of ethanol. ICS 205-930 (0.56, 1.0, 3.0, 10.0, and 17.0 mg/kg i.p.) was examined on ethanol and water self-administration in an operant paradigm. Following a sucrose-fading procedure, two groups of nondeprived rats responded on either a concurrent fixed ratio 4 schedule for ethanol (10% v/v) and water (CONC FR4 FR4), or a single FR4 schedule for ethanol (10% v/v). ICS 205-930 dose-dependently decreased ethanol-reinforced responding in the concurrent condition without decreasing water-reinforced responding, suggesting a specific effect on ethanol. Ethanol-reinforced responding was also dose-dependently decreased in the single FR4 condition, but the dose effect curve was shifted to the left. These data support the conclusions that 5-HT3 systems may play a specific role in ethanol self-administration that is independent of general appetitive and motor processes, and that 5-HT3 antagonists may have therapeutic efficacy in the treatment of alcohol abuse when multiple reinforcers are available.
Alcohol Drinking↗
Ethanol self-administration by alcohol-nonpreferring (NP) rats in a continuous access situation.
Male rats, from the alcohol nonpreferring (NP) line, were studied in operant chambers in which food pellets, water, and 10% ethanol (v/v) were available continuously for 23 h/d. The NP rats consumed less ethanol per day following 7 weeks under these conditions than did either alcohol-preferring (P) rats or Long-Evans (LE) studied previously under the same conditions for 4 weeks. The NP rats consumed 0.2 g/kg per day during the first week of the experiment, 0.72 g/kg per day during the fourth week, and 1.03 g/kg per day during the seventh week compared to 2.2 g/kg per day for LE rats and 4.8 g/kg per day for P rats following 4 weeks. These data indicate that NP rats will slowly initiate ethanol self-administration under continuous access conditions, but to a lesser extent and at a slower rate than other lines of rats studied previously.
Alcoholism↗
Home-cage ethanol consumption and motor activity: lack of relation to either initial activity or amphetamine-induced locomotion.
In two separate studies, the relationship between home-cage, two bottle ethanol/water consumption and both initial motor reactivity to a novel environment and amphetamine induced motor activity was determined in nonselected Wistar rats. In neither study was any correlation found. While home-cage ethanol consumption may not be an accurate measure of ethanol self-administration, the studies suggest that unlike reports for other drugs of abuse, there does not appear to be a simple relationship between alcohol preference and motor activity.
Alcohol Drinking↗
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.
Animals↗
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.
Animals↗
Muscimol injected into the medial prefrontal cortex of the rat alters ethanol self-administration.
The role of the rodent prefrontal cortex in the regulation of ethanol self-administration has not been widely explored. Understanding the role of GABAergic transmission in this area in relation to ethanol self-administration is important, as the GABA system may be one of several targets for alcohol's actions in the brain. Rats were initiated to drink 10% ethanol from a dipper using a sucrose-substitution procedure. When baseline behavior was stable, bilateral microinjections of muscimol (a GABA(A) agonist) into the prefrontal cortex were tested at doses of 17.5, 30, 100 and 300 ng/microl. Ethanol self-administration was decreased by approximately 40% at the 30-ng dose and 30% at the 100-ng dose. No effects were observed at either the 17.5- or 300-ng dose. The effect on the pattern of self-administration was to shorten the size of the first run of drinking without affecting the rate of drinking. The hypothesis is put forward that the injections increased glutamatergic output to the nucleus accumbens (nAcc) that in turn increased accumbens output. This increased output is proposed as similar to the effects of dopaminergic (DA) manipulations within this system.
Alcohol Drinking↗
Dopaminergic and opiate agonists and antagonists differentially decrease multiple schedule responding maintained by sucrose/ethanol and sucrose.
Similar neurobiological mechanisms are hypothesized to influence ethanol- and food-related reinforcement processes. This study examined the ability of compounds with dopaminergic or opiate activity to selectively alter responding maintained by a sucrose/ethanol solution in comparison to a sucrose solution. Long-Evans rats were trained to press a lever using 5% sucrose/10% ethanol and 5% sucrose as the reinforcers on a multiple Fixed Ratio 4 Fixed Ratio 4 schedule of reinforcement. When stable responding was established, the effects of intraperitoneally administered amphetamine (0.0-3.0 mg/kg), haloperidol (0.0-1.0 mg/kg), morphine (0.0-10.0 mg/kg), and naloxone (0.0-10.0 mg/kg) were examined on total session reinforcer presentation and presentation of each reinforcer within individual multiple schedule components. Prior to drug treatment, the total number of reinforcer presentations of the sucrose/ethanol solution was significantly greater than sucrose reinforcer presentations, suggesting the sucrose/ethanol solution was a more efficacious reinforcer. All agents administered decreased responding maintained by sucrose/ethanol and sucrose. The dose-effect curves for sucrose/ethanol were shifted to the left compared to sucrose, suggesting that although the compounds did not selectively impact sucrose/ethanol-maintained responding, sucrose/ethanol-maintained responding was more sensitive to the effects of these compounds.
Amphetamine↗
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.
Alcohol Drinking↗