Chlordiazepoxide effects on ethanol self-administration: dependence on concurrent conditions.

Experiments examined the effects of acute doses of chlordiazepoxide upon ethanol self-administration in the rat. A concurrent-schedule procedure was used that employed choice between ethanol (5%) and a second fluid (either water or a 1% sucrose solution). When ethanol and water were the available fluids, chlordiazepoxide at doses of 15 and 20 mg/kg reduced ethanol-reinforced responding and intake, with a greater reduction occurring at the 20 mg/kg dose. However, when ethanol and sucrose were concurrently available, in many rats only the 20 mg/kg dose of chlordiazepoxide reduced ethanol-reinforced responding. The differences in dose response function occurred in most animals without large changes in the baseline ethanol-reinforced responding across the two concurrent conditions. Thus the dose-effect curve relating chlordiazepoxide and ethanol self-administration can be altered, dependent upon the nature of the concurrently available reinforcers.     

Concurrent phencyclidine and saccharin access: presentation of an alternative reinforcer reduces drug intake.

Six monkeys self-administered orally delivered phencyclidine ("angel dust") and saccharin under concurrent fixed-ratio 16 schedules during daily three-hour sessions. Liquid deliveries were contingent upon lip-contact responses on solenoid-operated drinking spouts. Three saccharin concentrations (0.003%, 0.03% and 0.3%, wt/vol) were tested in a nonsystematic order. For each saccharin concentration, the following series of phencyclidine concentrations (mg/ml) was presented: 0.25, 0.5, 1, 0.25 (retest), 0.125, 0.0625, 0.0312, 0.25 (retest) and 0 (water with stimuli signaling phencyclidine). As the saccharin concentration increased, the number of drug deliveries decreased, and the peaks of the concentration-response functions were shifted to the right. The lowest saccharin concentration (0.003%, wt/vol) maintained responding in excess of phencyclidine levels in only one monkey. The two higher saccharin concentrations maintained behavior far in excess of phencyclidine, but saccharin deliveries decreased in some monkeys as phencyclidine concentration and intake (mg/kg) increased. The time course and patterns of phencyclidine-reinforced responding were also altered when saccharin was concurrently available. The results are discussed in terms of strategies to reduce drug-reinforced behavior, preference between different reinforcers, and measures of reinforcing efficacy.     

Drug discrimination in rats under concurrent variable-interval variable-interval schedules

Eight rats were trained to discriminate pentobarbital from saline under a concurrent variable-interval (VI) VI schedule, on which responses on the pentobarbital-biased lever after pentobarbital were reinforced under VI 20 s and responses on the saline-biased lever were reinforced under VI 80 s. After saline, the reinforcement contingencies programmed on the two levers were reversed. The rats made 62.3% of their responses on the pentobarbital-biased lever after pentobarbital and 72.2% on the saline-biased lever after saline, both of which are lower than predicted by the matching law. When the schedule was changed to concurrent VI 50 s VI 50 s for test sessions with saline and the training dose of pentobarbital, responding on the pentobarbital-biased lever after the training dose of pentobarbital and on the saline-biased lever after saline became nearly equal, even during the first 2 min of the session, suggesting that the presence or absence of the training drug was exerting minimal control over responding and making the determination of dose-effect relations of drugs difficult to interpret. When the pentobarbital dose-response curve was determined under the concurrent VI 50-s VI 50-s schedule, responding was fairly evenly distributed on both levers for most rats. Therefore, 6 additional rats were trained to respond under a concurrent VI 60-s VI 240-s schedule. Under this schedule, the rats made 62.6% of their responses on the pentobarbital-biased lever after pentobarbital and 73.5% of their responses on the saline-biased lever after saline, which also is lower than the percentages predicted by perfect matching. When the schedule was changed to a concurrent VI 150-s VI 150-s schedule for 5-min test sessions with additional drugs, the presence or absence of pentobarbital continued to control responding in most rats, and it was possible to generate graded dose-response curves for pentobarbital and other drugs using the data from these 5-min sessions. The dose-response curves generated under these conditions were similar to the dose-response curves generated using other reinforcement schedules and other species.     

Drug discrimination under two concurrent fixed-interval fixed-interval schedules

Pigeons were trained to discriminate 5.0 mg/kg pentobarbital from saline under a two-key concurrent fixed-interval (FI) 100-s FI 200-s schedule of food presentation, and later tinder a concurrent FI 40-s FI 80-s schedule, in which the FI component with the shorter time requirement reinforced responding on one key after drug administration (pentobarbital-biased key) and on the other key after saline administration (saline-biased key). After responding stabilized under the concurrent FI 100-s FI 200-s schedule, pigeons earned an average of 66% (after pentobarbital) to 68% (after saline) of their reinforcers for responding under the FI 100-s component of the concurrent schedule. These birds made an average of 70% of their responses on both the pentobarbital-biased key after the training dose of pentobarbital and the saline-biased key after saline. After responding stabilized under the concurrent FI 40-s FI 80-s schedule, pigeons earned an average of 67% of their reinforcers for responding under the FI 40 component after both saline and the training dose of pentobarbital. These birds made an average of 75% of their responses on the pentobarbital-biased key after the training dose of pentobarbital, but only 55% of their responses on the saline-biased key after saline. In test sessions preceded by doses of pentobarbital, chlordiazepoxide, ethanol, phencyclidine, or methamphetamine, the dose-response curves were similar under these two concurrent schedules. Pentobarbital, chlordiazepoxide, and ethanol produced dose-dependent increases in responding on the pentobarbital-biased key as the doses increased. For some birds, at the highest doses of these drugs, the dose-response curve turned over. Increasing doses of phencyclidine produced increased responding on the pentobarbital-biased key in some, but not all, birds. After methamphetamine, responding was largely confined to the saline-biased key. These data show that pigeons can perform drug discriminations under concurrent schedules in which the reinforcement frequency under the schedule components differs only by a factor of two, and that when other drugs are substituted for the training drugs they produce dose-response curves similar to the curves produced by these drugs under other concurrent interval schedules.     

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.     

Reinforcing effects of caffeine in coffee and capsules.

In a residential research ward the reinforcing and subjective effects of caffeine were studied under double-blind conditions in volunteer subjects with histories of heavy coffee drinking. In Experiment 1, 6 subjects had 13 opportunities each day to self-administer either a caffeine (100 mg) or a placebo capsule for periods of 14 to 61 days. All subjects developed a clear preference for caffeine, with intake of caffeine becoming relatively stable after preference had been attained. Preference for caffeine was demonstrated whether or not preference testing was preceded by a period of 10 to 37 days of caffeine abstinence, suggesting that a recent history of heavy caffeine intake (tolerance/dependence) was not a necessary condition for caffeine to function as a reinforcer. In Experiment 2, 6 subjects had 10 opportunities each day to self-administer a cup of coffee or (on different days) a capsule, dependent upon completing a work requirement that progressively increased and then decreased over days. Each day, one of four conditions was studied: caffeinated coffee (100 mg/cup), decaffeinated coffee, caffeine capsules (100 mg/capsule), or placebo capsules. Caffeinated coffee maintained the most self-administration, significantly higher than decaffeinated coffee and placebo capsules but not different from caffeine capsules. Both decaffeinated coffee and caffeine capsules were significantly higher than placebo capsules but not different from each other. In both experiments, subject ratings of "linking" of coffee or capsules covaried with the self-administration measures. These experiments provide the clearest demonstrations to date of the reinforcing effects of caffeine in capsules and in coffee.     

Differential effects of pentobarbital and cocaine on punished and nonpunished responding.

Similar rates of punished and nonpunished responding, maintained with equated rates of reinforcement, were established in pairs of rats. One subject of each pair was exposed to a random-ratio schedule of food presentation. The interreinforcement intervals for this subject comprised the intervals of a random-interval schedule of reinforcement for the other (yoked) rat. The random-ratio schedule maintained rates of responding higher than those maintained by the same rate of reinforcement schedule according to the yoked random-interval contingency. A random-ratio schedule of electric foot shock added to the random-ratio schedule of food presentation suppressed rates of responding such that similar rates of responding were observed in rats of both groups. Pentobarbital (3.0 to 17.0 mg/kg) increased punished responding at doses that had little effect on or decreased nonpunished responding, whereas cocaine (5.6 to 30 mg/kg) increased nonpunished responding at doses that decreased or did not alter punished responding. Qualitatively different effects of pharmacological agents on punished and nonpunished responding can be obtained using procedures that generate similar rates and temporal patterns of punished and nonpunished responding. The effects of pentobarbital and cocaine on responding can be determined by factors other than simply the baseline rate of responding.     

Drug effects on fixed-interval responding with pause requirements for food presentation.

In pigeons performing under a multiple schedule of food presentation, low key-pecking rates (0.18 to 0.29 responses per second) were maintained during 3-min fixed-interval components by requiring a 4-, 5-, or 6-sec pause preceding the food-delivery response (tandem DRL), while higher rates (0.70 to 1.37 responses per second) were maintained in alternative fixed-interval components by requiring a pause of no more than 40 msec preceding the food-delivery response (tandem DRH). Thus, reinforcement density was equal but overall response rates markedly different in the two schedule components. Pentobarbital (3, 10 mg/kg) had effects on overall rates of responding consistent with a rate-dependency interpretation (low rates were increased while higher rates were decreased), but d-amphetamine (0.03 to 3 mg/kg) either failed to increase low overall rates in the tandem DRL components or increased them only slightly. Effects of both drugs on local responding within the fixed-intervals were always related in an orderly way to control response rate, but the extent of rate increases produced by d-amphetamine was modifed in some birds by pause requirements such that the drug increased comparable rates less when these occurred in the tandem DRL component than when they occurred in the tandem DRH components. Control rate is an important determinant of drug effects, independent DRH components. Control rate is an important determinant of drug effects, independent of reinforcement density maintaining rates, and independent of environmental influences, such as response-spacing requirements for food presentation, that can modify the extent of some drug-produced rate changes.     

Punishment of responding under schedules of stimulus-shock termination: effects of d-amphetamine and pentobarbital.

Responding maintained in squirrel monkeys under 5-min fixes-interval schedules of either food presentation or termination of a visual stimulus associated with electric-shock delivery was suppressed by presenting an electric shock for every thirtieth response (punishment). In monkeys responding under the schedule of food presentation, d-amphetamine sulfate only further decreased punished responding, and pentobarbital sodium markedly increased punished responding, as expected from previous reports. In monkeys responding under the schedule of stimulus-shock termination, however, the effects of the two drugs were opposite: d-amphetamine markedly increased punished responding, whereas pentobarbital only decreased responding. Thus, the effects of these drugs on punished responding were different depending on the type of event maintaining responding. These and previous results indicate that it may be misleading and inaccurate to speak of the effects of drugs on "punished responding" as though punishment were a unitary phenomenon. As with any behavior, the effects of drugs and other interventions on punished responding cannot be accurately characterized independently of the precise conditions under which the behavior occurs.     

Effects of promazine, chlorpromazine, d-amphetamine, and pentobarbital on treadle pressing by pigeons under a signalled shock-postponement schedule.

The effects of promazine on treadle pressing to postpone the presentation of electric shock were studied in three pigeons. The effects of chlorpromazine, d-amphetamine, and pentobarbital were studied in two of these pigeons. Each treadle press postponed electric shock for 20 sec and presentation of a preshock stimulus for 14 sec. Selected doses of both promazine and chlorpromazine increased the rates of treadle pressing in all birds. The response-rate increases produced by promazine and chlorpromazine were due to increased conditional probabilities of treadle pressing both before and during the preshock stimulus. d-Amphetamine (1 and 3 mg/kg) slightly increased responding in one of the birds, but not to the extent that promazine or chlorpromazine did. In the other bird, the 10 mg/kg dose of d-amphetamine increased shock rate but did not change response rate. Some doses of d-amphetamine increased the conditional probabilities of responding both in the absence of the preshock signal and during the preshock signal in both birds. Pentobarbital only decreased response rates and increased shock rates.