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R A Meisch

Publications and source records attributed to R A Meisch.

At least 55 records · Page 3Linked to original sources
PubMed1990

Ethanol self-administration in long sleep and short sleep mice indicates reinforcement is not inversely related to neurosensitivity.

Studies of ethanol drinking suggest an inverse correlation between innate sensitivity to ethanol and behavior reinforced by this drug. The present study investigated ethanol reinforced behavior in mice selectively bred for high, Long Sleep/Institute for Behavioral Genetics (LS), and low, Short Sleep/Institute for Behavioral Genetics (SS), sensitivity to ethanol. Results show that both lines will drink large amounts of ethanol postprandially. However, in the absence of food presentation, LS and SS mice differed significantly in ethanol reinforced behavior. Ethanol maintained higher rates of responding, greater intake and higher blood ethanol levels in LS relative to SS mice across increasing fixed-ratio values. Ethanol did not maintain fixed-ratio lever pressing above rates maintained by vehicle in SS mice. Responding for and consumption of 8% ethanol significantly exceeded that of vehicle only in LS mice. Response rates of LS mice showed a typical inverted U-shaped relationship to ethanol concentration. Postsession blood ethanol levels and body temperatures indicated pharmacologically significant ethanol intake only in LS mice. Thus, ethanol served as an effective reinforcer in LS mice across a range of environmental conditions. Conversely, ethanol was not established as a positive reinforcer in SS mice under any of the broad range of conditions studied. These results are not consistent with the frequently reported negative correlation between ethanol intake and sensitivity to ethanol and rule out a causal basis for correlations seen between these traits.

Animals↗
PubMed1989

Oral pentobarbital intake in rhesus monkeys: effects of drug concentration under conditions of food deprivation and satiation.

Pentobarbital-reinforced behavior was studied in four rhesus monkeys. A pentobarbital solution and water were concurrently available during 3-hr sessions; water was freely available between sessions. Both pentobarbital concentration and feeding conditions (deprivation versus satiation) were varied. In two food-restricted monkeys subsequent food satiation eliminated pentobarbital-maintained responding. In two other food-restricted monkeys the effects of food satiation varied with the drug concentration. At the highest concentration, 4 mg/ml, food satiation did not alter responding, whereas at 2 mg/ml a moderate decrease occurred and at 1 mg/ml responding was greatly reduced. During the food satiation phase, when the concentration was 4 mg/ml, responding was well maintained under several fixed-ratio sizes. Large quantities of pentobarbital were consumed, and intoxication was observed. Water-maintained responding occurred at low rates and did not vary across feeding conditions or drug concentration. The results support an interpretation in terms of a behavioral mechanism of action. Specifically, the effects of food deprivation on drug self-administration are to increase the magnitude of the reinforcing effects of the drug.

Administration, Oral↗
PubMed1989

Oral self-administration of pentobarbital by rhesus monkeys: maintenance of behavior by different concurrently available volumes of drug solution.

For 4 rhesus monkeys, mouth-contact responses with either of two brass spouts were reinforced according to fixed-ratio schedules by 0.65-mL liquid deliveries during daily 3-hr sessions. Three experiments were conducted. In each experiment, independent fixed-ratio schedules were concurrently in effect at the two spouts. Following completion of each fixed ratio on a spout, a specified number of liquid deliveries were available from that spout under a continuous-reinforcement schedule. The number of such deliveries available at each spout was manipulated independently. In Experiment 1, a 1-mg/mL pentobarbital solution was simultaneously available with water (the drug vehicle) under concurrent fixed-ratio schedules of 32 responses for 3 subjects and 64 responses for the remaining subject. The number (N) of liquid deliveries that were available after completion of each fixed ratio was varied in the following order: 8, 4, 2, 1, and 8 (retest). For each subject at each condition, drug maintained more responding than water. The number of drug deliveries obtained per session was directly related to the amount of drug available per fixed ratio (i.e., to N), whereas the number of fixed ratios completed per session generally was inversely related to the value of N. In Experiment 2, fixed-ratio size was the same for each subject as in Experiment 1, but deliveries of a 1-mg/mL pentobarbital solution were available at both spouts. The number of drug deliveries available under one fixed-ratio schedule (Ns, the "standard" reinforcer amount) was held at eight, and the number of drug deliveries available under the second schedule (Nc, the "comparison" reinforcer amount) was changed across blocks of six sessions of stable responding in the following order: 1, 2, 4, 8, 4, 2, and 1. The identical series of comparison reinforcer amounts (Nc) was then tested twice more, but with the standard reinforcer (Ns) held first at four and then at two deliveries. Across the three choice series, reinforcing effects were directly related to reinforcer magnitude. In Experiment 3, deliveries of a 1-mg/mL pentobarbital solution again were available at both spouts. However, the two reinforcer amounts were held constant at N = 8 deliveries under one schedule and N = 4 deliveries under the second schedule, and fixed-ratio size was systematically varied. Across the range of fixed-ratio sizes from low to high, the degree to which behavior was better maintained by the larger of the two drug quantities was an inverted U-shaped function of fixed-ratio size.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Fixed-ratio schedules of oral ethanol self-administration in inbred mouse strains.

Previous studies of ethanol reinforcement in BALB/cJ and C57BL/6J mice have shown that over a range of concentrations oral ethanol appeared to serve as a reinforcer only for the C57BL/6J mice. In the previous studies BALB/cJ mice maintained rates of responding for ethanol that only slightly exceeded the rates maintained by the vehicle, water. However, the quantity of ethanol consumed with the continuous reinforcement schedule (fixed ratio one) may have led to pharmacologically significant effects, given the high sensitivity to ethanol of this genotype. The present study tested whether and to what extent ethanol would maintain responding under increasing fixed ratio size in these two strains of mice at ethanol concentrations of 0%, 8%, and 16% (w/v). For the C57BL/6J mice, as fixed-ratio size increased from 1 to 2, 4, and 8, there were almost directly proportional increases in response rate at ethanol concentrations of 8% and 16% (w/v), but not at 0%. Post-session blood ethanol levels confirmed intake of pharmacologically significant quantities. The volume consumed per unit of body weight decreased as fixed-ratio size increased. For the BALB/cJ mice, at no condition did ethanol maintain responding at levels that significantly exceeded vehicle maintained responding. BALB/cJ mice did not differ from C57BL/6J mice as fixed-ratio size was increased during vehicle conditions. These results, along with earlier findings, demonstrate that ethanol can serve as a reinforcer for C57BL/6J mice but not in BALB/cJ mice over a range of schedule conditions. They further support the conclusion that genotype is an important determinant of ethanol reinforced behavior.

Alcohol Drinking↗
PubMed1988

Oral self-administration of pentobarbital by rhesus monkeys: relative reinforcing effects under concurrent fixed-ratio schedules.

During daily 3-hr sessions, orally delivered pentobarbital solutions and water, or two separate pentobarbital solutions, were concurrently available to rhesus monkeys according to fixed-ratio schedules of mouth contacts with a spout. First water, and then each of four "comparison-concentration" pentobarbital solutions (0.0625, 0.25, 1, and 4 mg/mL), was successively available from one spout for a block of sessions under a fixed-ratio-64 (three monkeys) or fixed-ratio-16 (one monkey) schedule. Under an identically sized fixed-ratio schedule, deliveries of a "standard-concentration" pentobarbital solution were concurrently available from a second spout. The concentration of the standard solution remained unchanged throughout testing of the series of comparison solutions. Each of three pentobarbital concentrations (4, 1, and 0.25 mg/mL) in turn served as the standard concentration. Within each pair of concurrently available solutions, the higher drug concentration maintained more behavior than the lower concentration. Thus when monkeys were provided with concurrent access to different pentobarbital concentrations, relative reinforcing effects were directly related to drug concentration. Further, the amount of behavior maintained by a particular drug concentration was dependent on the concentration of the concurrently available drug solution. Thus, the relative effectiveness of a reinforcer in maintaining behavior is a function of both the reinforcer's magnitude and the availability of alternative reinforcers in the environment.

Administration, Oral↗
PubMed1988

Differential establishment and maintenance of oral ethanol reinforced behavior in Lewis and Fischer 344 inbred rat strains.

Oral ethanol self-administration was investigated systematically in two inbred strains of rats, Fischer 344 CDF (F-344)/CRLBR (F344) and Lewis LEW/CRLBR (LEW). For both strains ethanol maintained higher response rates and was consumed in larger volumes than the water vehicle. In addition, blood ethanol levels increased with increases in ethanol concentration. However, LEW rats drank substantially more ethanol than F344 rats. The typical inverted U-shaped function between ethanol concentration and number of deliveries was observed for the LEW rats, whereas for the F344 rats much smaller differences were seen between ethanol and water maintained responding. For the LEW strain, as the fixed-ratio size was increased, the number of responses increased almost in direct proportion to the fixed-ratio size increase, so that at least at the lower fixed-ratio values the rats were obtaining similar numbers of deliveries at different fixed-ratio sizes. However, a decrease in ethanol deliveries and blood ethanol levels was observed at higher fixed-ratio sizes. Similar results were obtained in F344 rats, but the amount of responding was lower and less consistent. LEW rats showed significantly higher response rates, numbers of ethanol deliveries and blood ethanol levels. Ethanol-induced behavioral activation also was observed in LEW rats, but not in F344 rats. These results support the conclusion that ethanol serves as a strong positive reinforcer for LEW rats and as a weak positive reinforcer for F344 rats, and that genotype is a determinant of the degree to which ethanol functions as a reinforcer.

Animals↗
PubMed1987

Factors controlling drug reinforced behavior.

An overview is provided of factors controlling drug reinforced behavior. Drug reinforced behavior is defined, and control procedures for rigorously identifying such behavior are discussed. Factors affecting drug reinforced behavior include the drug itself, animal species, route of administration, current circumstance variables, subject's experimental history, and response consequences. Current circumstance variables concern conditions present during opportunities for drug self-administration and include such factors as stimulus control, food deprivation, drug-access conditions, and brain lesions. Response consequence variables include reinforcement schedule, punishment, drug dose, and competing reinforcers. Drug reinforced behavior is a member of a more general class of behavior, namely operant behavior. Over the last 25 years there has been a rapid increase in understanding drug reinforcement, and this pattern of expanding knowledge suggests that the high rate of progress will continue.

Animals↗
PubMed1987

Genetic differences in the development of physical dependence on pentobarbital in four inbred strains of rats.

Fischer 344 (F344), Lewis (LEW), spontaneously hypertensive (SHR) and Wistar Kyoto (WKY) rats were chronically fed food containing pentobarbital on an escalating drug dosage schedule over a period of 47 days. During treatment, the growth curve in LEW, SHR and WKY rats was suppressed as compared with the respective controls. Motor incoordination was evaluated by a rotarod performance test. The ranking of the motor incoordination was as follows: WKY much greater than LEW greater than SHR greater than F344. After substitution of normal food for the pentobarbital-admixed food, various signs of pentobarbital withdrawal occurred. The withdrawal signs from pentobarbital in F344, LEW and SHR rats were mild as compared with those in WKY rats. The order of the severity of withdrawal signs in four inbred strains was parallel to that for motor incoordination. These results suggest that the differences between strains in withdrawal can be attributed to differences in the degree of chronic CNS depression produced by pentobarbital.

Animals↗
PubMed1986

Oral ethanol reinforced behavior in inbred mice.

The use of genetically defined animals in many areas of alcohol research provides valuable information about the contribution of genetic factors to ethanol-related behaviors. Utilizing the principles of operant conditioning, we determined whether mice which are known for high ethanol preference, C57BL/6J males, would orally self-administer this substance. Strategies used with other species were successful in inducing pharmacologically significant blood alcohol levels and in establishing ethanol as a reinforcer in this mouse strain. Responding for and consumption of 8% (w/v) ethanol exceeded baseline levels of responding for water. This species and method may prove useful in determining the genetic relationship among various ethanol-related behaviors and their mechanisms of action and in studies of behavior reinforced by drugs.

Animals↗
PubMed1986

Genetic differences in the establishment of ethanol as a reinforcer.

Ethanol, self-administered orally, has been shown to serve as an effective reinforcer in several species. Self-administration studies have also illustrated that ethanol-drinking behavior can be conceptualized as a specific type of operant behavior. The use of inbred and selectively bred animals in other areas of alcohol research has provided valuable information about the contribution of genetic factors to ethanol-related behaviors. Our research was designed to study genetic differences in oral self-administration in the ALKO AA (Alcohol Accepting) and ANA (Alcohol Non-Accepting) rat lines, selected for ethanol preference. Thus, we applied a behavior genetic analysis to aid in determining the contribution of genetic factors to behavior, specifically drug-seeking behavior. The results of our experiments indicate that genetic differences are important factors contributing to the establishment of a drug as a reinforcer. At least in the case of ethanol, the drug did not act as a reinforcer in non-preferring animals. Conversely, in preferring animals, ethanol was readily established as a reinforcer.

Alcohol Drinking↗
PubMed1985

Oral drug self-administration in rhesus monkeys: interactions between drug amount and fixed-ratio size.

During daily 3-hr sessions, 5 rhesus monkeys drank drug solutions and water that were concurrently available. The drug solutions were: 1 milligram per milliliter (mg/mL) pentobarbital (2 monkeys), 1 mg/mL pentobarbital plus 0.5% ethanol (1 monkey), 1 mg/mL pentobarbital plus 1% ethanol (1 monkey), and 8% ethanol (1 monkey). The drug solution and water were available under identical two-component tandem fixed-ratio continuous-reinforcement N schedules. Two variables were manipulated: the size of the fixed-ratio component and the number of liquid deliveries (N) in the second component. Deliveries of the drug solution maintained higher rates of responding than did deliveries of the drug vehicle, water. The number of drug deliveries per session increased with increases in the number of deliveries per fixed ratio and decreased with increases in fixed-ratio size. Analysis of the results in terms of the proportion of deliveries to responses showed that the number of drug deliveries per session was directly related to the size of this quotient. Finally, when fixed-ratio size was repeatedly doubled, the following orderly relationship emerged: The greater the number of available drug deliveries per fixed ratio, the less was the percent decrease in the number of fixed ratios completed per session. It was concluded that increases in the number of liquid deliveries per fixed ratio resulted in increases in reinforcing efficacy.

Animals↗
PubMed1984

Self-administration of orally-delivered methohexital in rhesus monkeys with phencyclidine or pentobarbital histories: effects of food deprivation and satiation.

Orally-delivered methohexital was demonstrated to function as a reinforcer for rhesus monkeys with either phencyclidine or pentobarbital self-administration histories. The effects of food deprivation and food satiation were compared across a wide range of methohexital concentrations. Initially, three monkeys were trained to orally self-administer phencyclidine (0.25 mg/ml) and water, and three were trained to orally self-administer pentobarbital (0.5 mg/ml) and water under concurrent fixed-ratio (FR) schedules during daily 3-hr sessions. Liquid deliveries during the session (drug and water) and intersession (water) were contingent upon lip contact responses on solenoid-operated drinking spouts. The monkeys were first tested while food deprived by maintaining them at 85% of their free-feeding body weights. Methohexital concentrations were presented in the following order, and each concentration was held constant until at least five or six sessions of stable behavior were obtained: 2, 2.8, 4, 2 (retest), 1, 0.5, (plus 0.25 and 0.125 in monkey M-W) and 2 (retest) mg/ml. The monkeys were then food satiated by allowing them unlimited access to food, and the methohexital concentration series was repeated. During food deprivation, the concentration-response functions generally resembled an inverted U. Concurrent water-maintained responding was generally low, but it increased in some monkeys as methohexital concentrations increased in some monkeys. During food satiation, methohexital-maintained responding was not different from water-maintained responding in some monkeys, but in others it was substantially higher than water-maintained responding. Maximum drug intake ranged from 20.4 to 93.8 mg/kg during food deprivation and from 6.4 to 64.2 during food satiation among the six monkeys.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1984

Pentobarbital self-administration in rhesus monkeys: drug concentration and fixed-ratio size interactions.

Performances of three rhesus monkeys were reinforced by the oral delivery of pentobarbital and studied as functions of fixed-ratio size and drug concentration. Pentobarbital solutions and water were concurrently available on identical reinforcement schedules from separate liquid-delivery systems during 3-hour sessions. Under a fixed-ratio 16 schedule of drug availability, a descending series of drug concentrations was tested (4, 2, 1, 0.5, 0.25, 0.125, and 0.0625 mg/ml, followed by a retest at 4 mg/ml). Partial concentration series beginning with the highest concentration were repeated with fixed-ratios of 32 and 64, with a fixed-ratio 128 for two monkeys, and with fixed-ratio 256 for one. At each fixed-ratio value, response rate and number of drug deliveries were inverted U-shaped functions of pentobarbital concentration. Drug intake (mg/kg/session) increased directly with drug concentration. As the fixed-ratio size was increased, the number of liquid deliveries decreased. For each drug concentration, when the numbers of drug deliveries at fixed-ratios of 32, 64, and 128 responses were plotted as percentages of those obtained at fixed-ratio 16, the following orderly relationship emerged: the higher the drug concentration, the less that drug deliveries were decreased by increases in fixed-ratio size. This relationship indicates an increase in reinforcing efficacy with increases in pentobarbital concentration.

Animals↗
PubMed1983

Effects of minimum-interreinforcer interval on ethanol-maintained performance of rats.

Dipper cups filled with an 8% (w/v) ethanol solution were presented to Long-Evans hooded rats according to either a multiple Extinction chi sec Fixed-Ratio 1 or a chain Differential-Reinforcement-of-Other-Behavior chi sec Fixed-Ratio 1 schedule or reinforcement. The scheduled value of the extinction and differential-reinforcement-of-other-behavior components was varied to manipulate minimum-interreinforcer interval. Minimum-interreinforcer intervals from 0 sec (baseline condition of continuous reinforcement) to 480 sec were tested in an ascending series followed by a descending, retest series. Increasing the minimum-interreinforcer interval reduced the number of ethanol presentations obtained under both reinforcement schedules. These reductions were not due to ceiling effects imposed by the maximum number of possible deliveries obtainable within a session. The number of ethanol presentations obtained was always less than the maximum number of possible deliveries obtainable within a session. The number of ethanol presentations obtained was always less than the maximum number permitted by the value of the minimum-interreinforcer interval. Thus, imposing minimum-interreinforcer intervals between drinking opportunities reduces the level of ethanol self-administration relative to continuous-access baseline conditions.

Alcohol Drinking↗
PubMed1982

Orally delivered pentobarbital as a reinforcer for rhesus monkeys with concurrent access to water: effects of concentration, fixed-ratio size, and liquid positions.

The number of liquid deliveries and pattern of concurrent pentobarbital and water drinking were studied in three food deprived rhesus monkeys during daily 3-hr sessions. During the daily sessions, deliveries of approximately 0.6 ml of each liquid occurred under fixed-ratio (FR) schedules of lip contact responses. Between sessions water was freely available. Session drinking was studied as a function of pentobarbital concentration (1.0, 1.41, 2.0, and 4.0 mg/ml) and FR size (4, 8, 16 and 32 lip contacts per delivery). The number of drug deliveries decreased with increases in drug concentration. Drug intake ranged from 21 to 52 mg/kg of body wt./3-hr session. At all concentrations and FR values tested, the number of pentobarbital deliveries substantially exceeded the number of water deliveries. The positive reinforcing effect of the pentobarbital was indicated by a consistent choice of drug over water irrespective of the side position of pentobarbital and by higher rates of drug responding. Pentobarbital drinking occurred in a negatively accelerated pattern whereas water drinking did not have any consistent pattern. Marked intoxication followed bouts of drug drinking.

Administration, Oral↗