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R A Meisch

Publications and source records attributed to R A Meisch.

97 records · Page 6Linked to original sources

Ethanol self-administration in ALKO rats: I. Effects of selection and concentration.

The ALKO Alcohol Accepting (AA) rats and Alcohol Non-Accepting (ANA) rats were used to study the relationship between ethanol preference in a two-bottle choice paradigm and oral ethanol self-administration in an operant conditioning paradigm. Ethanol served as a positive reinforcer in the preferring AA line. Under a continuous reinforcement schedule (FR 1), ethanol deliveries were consistently greater than water (vehicle) deliveries and varied as an orderly inverted U-shaped function of ethanol concentration. Conversely, in nonpreferring ANA animals, ethanol did not serve as a reinforcer. Findings obtained with the AA rats were compared with those obtained with Sprague-Dawley rats. Sprague-Dawley rats maintained higher levels of responding and greater ethanol intake, relative to AA rats, at all concentrations of ethanol tested. The data are consistent with evidence that genotype is a critical factor in determining the extent to which ethanol serves as a reinforcer. The results also suggest that ethanol preference and the maintenance of ethanol reinforced behavior under operant conditions appear to have some common mechanisms. However, since the selection for ethanol preference in AA rats apparently did not maximize the maintenance of ethanol-reinforced behavior in an operant paradigm, ethanol drinking behavior in the preference paradigm may not be completely generalizable to that observed in the operant model.

Animals↗

Ethanol self-administration in ALKO rats: II. Effects of selection and fixed-ratio size.

The ethanol-reinforced behavior of ALKO Alcohol Accepting (AA) rats was studied as a function of fixed-ratio (FR) size (1, 2, 4, 8 and 16) across several ethanol concentrations (8, 16 and 32% w/v). A comparison was also made with ethanol-reinforced behavior of Sprague-Dawley (SD) rats. Ethanol, previously shown to serve as a reinforcer in AA and SD rats, maintained responding in these animals under conditions of intermittent reinforcement. SD rats exhibited higher response rates than AA rats to obtain 8% ethanol concentrations as fixed-ratio size was varied in these experiments. These results confirm that, for AA rats, the selection for preference in a two-bottle choice situation did not include the selection for those biological factors which maximize ethanol-reinforced behavior under conditions of intermittent reinforcement. These experiments suggest the existence of distinct, biologically influenced components of ethanol drinking behavior, and have demonstrated several similarities as well as differences between two-bottle choice preference tests and operant studies of ethanol-reinforced behavior.

Animals↗

Cyclooxygenase inhibitors antagonize the rate-depressant effects of ethanol on fixed-ratio responding.

Prostaglandin synthetase inhibitors (PGSIs), which inhibit actions of the enzyme complex cyclooxygenase, significantly antagonize the effects of alcohols but not other sedative-hypnotics across a broad range of measures. This suggests that certain actions of alcohols, in particular ethanol, are mediated at least partially through a prostaglandin-related pathway. This study examined changes in the rate-depressant effects of ethanol in an operant task following pretreatment with either of two PGSIs, indomethacin (INDO) or aspirin (ASP). Water reinforcement maintained the responding of male Sprague-Dawley (SD) rats under a Fixed-Ratio (FR) 32 schedule. Saline, INDO or ASP had no significant effect on control rates of responding. INDO pretreatment significantly antagonized the rate-depressant effects of 1.0 and 1.5 g/kg ethanol. ASP pretreatment also resulted in significant antagonism of ethanol's rate-decreasing effects. INDO was more potent than ASP in antagonizing the rate-depressant effects of ethanol. These results provide further support for the hypothesis that alcohols, by fluidizing neuronal membranes and mobilizing the release of arachidonate, serve to increase prostaglandin production, resulting in some of the behavioral and physiological sequellae of ethanol administration.

Animals↗

Effects of feeding condition on orally delivered ethanol as a reinforcer for rhesus monkeys.

Twenty adult male rhesus monkeys could drink either or both an 8%-ethanol (w/v) solution or water during daily 3-h experimental sessions. Subjects were initially tested under ad lib feeding conditions, having received daily access to large amounts of food for approximately 8 months (Phase 1). The ethanol solution was concurrently available with its water vehicle under fixed-ratio schedules of mouth contacts with a drinking spout in which emission of 8 responses produced a liquid delivery (FR 8). Under these conditions ethanol served as a reinforcer for some subjects--it maintained higher response rates than water--but not for others. In the next experimental condition (Phase 2), subjects were again tested for ethanol self-administration under FR 8 schedules with water concurrently available, but while receiving daily food rations that maintained their body weights at less than what they had been under ad lib feeding conditions. Under these conditions all subjects self-administered ethanol at appreciable levels, but water-maintained responding also was at appreciable levels for some subjects. Increases in ethanol self-administration following institution of the reduced-feeding conditions in Phase 2 generally were inversely related to self-administration levels under the free-feeding conditions of Phase 1 (the greatest proportional increases in ethanol intake occurred with those monkeys that self-administered the least amount of ethanol in Phase 1). In Phase 3, the requirements of the concurrently operating fixed-ratio schedules delivering ethanol and water were increased to 16 responses (FR 16).(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗

Ethanol-reinforced responding of naive rhesus monkeys: acquisition without induction procedures.

Rodents will typically consume greater amounts of low concentration ethanol (1-6%) than water. However, few primate oral self-administration studies have examined low ethanol concentrations. Additionally, there is a scarcity of data showing ethanol-maintained behavior without using induction procedures in either rats or primates. In this study, 14, free-feeding, naive, adult, male rhesus monkeys were given access to a 2% (w/v) ethanol solution and vehicle (tap water) during daily 3-hour sessions. Water was freely available between sessions. Liquids were available under a concurrent fixed-ratio four reinforcement schedule; thus, four responses (mouth-spout contacts) on either spout were immediately followed by the delivery of approximately 0.65 ml of liquid. In phase 1, tap water was available from both spouts. In phase 2, vehicle and a 2% ethanol solution were concurrently available. The 2% ethanol solution maintained considerably higher response rates than vehicle for 12 of 14 monkeys. In phase 3, food intake was limited. During this phase, the 2% ethanol solution maintained significantly higher response rates than vehicle for all monkeys. Additionally, during phase 3, ethanol intakes were greater than those in phase 2 for all monkeys. Central drug effects and taste factors are discussed. These results demonstrate that ethanol will serve as a reinforcer for naive rhesus monkeys in the absence of induction procedures.

Alcohol Drinking↗

Ethanol reinforcement and its relationship to saccharin preference in Wistar rats.

Forty rats were given a choice between 0.1% sodium saccharin and water. Based on their intakes, three groups of six rats representing high, intermediate, and low saccharin preferences were selected. These rats were reduced to 80% of their free-feeding weights. Ethanol was established as a reinforcer by use of a food-induced drinking procedure. Between-group differences were assessed based on response rates across acquisition sessions (0, 1, 2, 4, 5.7, 8%, w/v), a fixed-ratio series (1, 2, 4, 8, 1), and a concentration series (8, 5.7, 4, 2, 2, 4, 5.7, 8, 11.3, 16, 22.6, 32, 8%, w/v). In 29 of 32 conditions which were analyzed, the mean number of responses for ethanol was higher for the high saccharin preference group than for the low, and in 25 of 32 conditions, the intermediate group fell between the high and the low. However, there was considerable variability within groups across all conditions, such that mean between-group differences were not significant. This variability may be reduced by considering diet preferences in addition to saccharin preference. Nonetheless, these results offer limited support for the increasing body of evidence indicating a relationship between the factors mediating ethanol self-administration and those involving ingestion of palatable foods and fluids.

Animals↗

Ethanol as an oral reinforcer in normal weight rhesus monkeys: dose-response functions.

Responding maintained by orally delivered ethanol was studied in three adult male rhesus monkeys with no previous drug-taking histories. The subjects had continuous access to water throughout the study and were fed sufficient food to maintain a positive caloric balance. During daily 3-h experimental sessions, ethanol solution and water were concurrently available under fixed-ratio reinforcement schedules from two liquid delivery systems that were mounted symmetrically on the side of the monkeys' cages. The positions of the ethanol and water alternated daily. A range of ethanol doses (1%, 2%, 4%, 5.7%, 8%, 11.3%, 16%, 22.7, and 32% w/v) was tested in ascending and descending order. Changes in concentration were made after six consecutive stable sessions. Generally, the number of ethanol deliveries increased and then decreased as the ethanol concentration was raised (an inverted U-shaped function). For two of the monkeys, ethanol deliveries exceeded water deliveries at concentrations from 1.0% to 5.7% w/v, whereas for a third monkey ethanol solution was preferred to water at concentrations as high as 16% w/v. Ethanol intake (g/kg) tended to increase linearly and then flatten as the concentration was raised. Blood ethanol levels, measured immediately following sessions in which 8% w/v ethanol was available, ranged from 45 to 146 mg/dl. Although no special training or acquisition procedures were used to establish responding, ethanol functioned as a reinforcer for each of the monkeys tested.

Animals↗