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31.
The effects of pentobarbital and d-amphetamine were studied in pigeons responding under several concurrent fixed-ratio variable-interval and concurrent fixed-ratio fixed-interval schedules of food presentation. Drug effects were compared with different fixed ratios, fixed and variable intervals, changeover delays, and with the schedules operating singly. Doses of d-amphetamine that increased or did not affect responding under the interval schedules decreased responding under the fixed-ratio schedule, whereas doses of pentobarbital that increased responding under the fixed-ratio schedule decreased or eliminated responding under the interval schedules. These effects depended both on the schedule of food delivery and the parameters of schedules arranged concurrently. Pentobarbital increased responding under the fixed-ratio schedule with 4-minute and 10-minute interval schedules arranged concurrently, but not with 1.5-minute schedules. d-Amphetamine decreased concurrent ratio and interval responding with the 1.5-minute interval schedules, but either increased or did not affect responding with the longer intervals. Changes in the parameter of one schedule altered responding controlled by that schedule and also other concurrent performances. As a consequence, the effects of drugs on each behavior were altered.  相似文献   
32.
Rates and patterns of key-press responding maintained under schedules in which responding resulted in intravenous injections of cocaine were studied in squirrel monkeys and rhesus monkeys. Each injection was followed by a 60- or 100-sec timeout period. Schedule-controlled behavior was obtained at appropriate cocaine doses in each species. Under FR 10 or FR 30 schedules, performance was characterized by high rates of responding (usually more than one response per second) in each ratio. Under FI 5-min schedules, performance was characterized by an initial pause, followed by acceleration of responding to a final rate that was maintained until the end of the interval. Under multiple fixed-ratio fixed-interval schedules, rates and patterns of responding appropriate to each schedule component were maintained. Responding seldom occurred during timeout periods under any schedule studied. At doses of cocaine above or below those that maintained characteristic schedule-controlled behavior, rates of responding were relatively low and patterns of responding were irregular. Characteristic fixed-interval responding was maintained over a wider range of cocaine doses than characteristic fixed-ratio responding. Complex patterns of responding controlled by discriminative stimuli under fixed-ratio or fixed-interval schedules can be maintained by cocaine injections in squirrel monkeys and rhesus monkeys.  相似文献   
33.
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.  相似文献   
34.
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.  相似文献   
35.
    
Six rhesus monkeys responding under a three-component multiple schedule were administered haloperidol to determine its effects on cocaine self-administration and on cocaine's disruptive effects on the repeated acquisition and performance of response chains. In the absence of haloperidol, 0.0032-0.032 mg/kg/infusion of cocaine increased response rate and the number of infusions in the self-administration component when compared to saline administration, whereas 0.1-0.32 mg/kg/infusion decreased response rate and the number of infusions. When compared to saline administration, the two lowest infusion doses of cocaine had little or no effect on responding in the acquisition and performance components; however, higher infusion doses of cocaine dose-dependently decreased response rate in these components. In addition, the higher doses of cocaine also increased the percentage of errors in the acquisition and performance components. Pretreatment with haloperidol (0.0032 or 0.01 mg/kg, i.m.) antagonized the effects of low doses of cocaine on the number of infusions in the self-administration component, whereas only the 0.01-mg/kg dose antagonized the effects of high doses of cocaine on the number of infusions. Neither dose of haloperidol antagonized the rate-decreasing effects of cocaine on responding in the acquisition and performance components significantly; the highest dose of haloperidol alone decreased rates of responding in each component. Antagonism of cocaine's error-increasing effects by haloperidol was only evident at one dose of cocaine (0.032 mg/kg/infusion), and was more complete in the performance components than in the acquisition components. Together, these data show the limited suitability of haloperidol for selectively antagonizing cocaine self-administration in the context of a multiple schedule involving transition behavior, and show the lack of uniform antagonism across operant behaviors.  相似文献   
36.
37.
    
Drugs with multiple actions can have complex discriminative‐stimulus properties. An approach to studying such drugs is to train subjects to discriminate among drug combinations and individual drugs in the combination so that all of the complex discriminative stimuli are present during training. In the current experiments, a four‐choice procedure was used to train pigeons to discriminate among dizocilpine (noncompetitive NMDA receptor blocker), pentobarbital (GABAA receptor agonist), a fixed‐dose combination of these two drugs, and saline. Following extended training, low doses of pentobarbital or dizocilpine administered alone produced saline‐appropriate responding. Higher doses of pentobarbital produced responding on the pentobarbital‐appropriate key and higher doses of dizocilpine produced responding on the dizocilpine key. Administering the lowest doses of pentobarbital and dizocilpine together resulted in responding on the saline‐appropriate key. Increasing the dose of pentobarbital in the presence of low doses of dizocilpine produced responding primarily on the pentobarbital‐appropriate key; increasing the dose of dizocilpine in the presence of the lowest dose of pentobarbital produced responding primarily on the dizocilpine‐appropriate key. Combining the higher doses of pentobarbital and dizocilpine resulted in responding primarily on the drug‐combination key. Low doses of phencyclidine or ethanol produced responding on the saline‐appropriate key, but intermediate doses resulted in individual subjects responding predominately on either the pentobarbital key, the dizocilpine key, or the drug‐combination key depending on the subject. After the highest dose of phencyclidine or ethanol, most subjects responded predominantly on the drug‐combination key. Low doses of other drugs tested produced responding on the saline‐appropriate key. With the highest diazepam doses responding was largely confined to the pentobarbital‐appropriate key. The highest doses of dextromethorphan or dextrorphan resulted in responding on the dizocilpine key more frequently than on other keys. Across a range of doses, morphine produced responding predominantly on the saline key. The results using the four‐key procedure emphasized the role of both GABAA and NMDA receptors in the complex discriminative stimulus properties of phencyclidine and of ethanol.  相似文献   
38.
Behavioral pharmacology has become increasingly independent of the experimental analysis of behavior. At its beginning, behavioral pharmacology was closely related to the experimental analysis of behavior, with developments in each field aiding the other. Early attempts to systematize data in behavioral pharmacology culminated with the development of the rate-dependency concept, but as this principle was found to have more limited generality than originally was hoped, a theoretical void developed. This circumstance was followed by increased reliance on pharmacological theory as a basis for experimentation and interpretation, with an attendant decrease in emphasis on environmental variables and behavioral interpretations. Lack of interplay between behavioral pharmacology and the experimental analysis of behavior is detrimental to both disciplines because each could contribute significantly to the other. The current trend might be reversed if more research were directed at elucidating behavioral mechanisms of drug action.  相似文献   
39.
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.  相似文献   
40.
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.  相似文献   
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