Selective antagonism of the error-increasing effect of morphine by naloxone in a repeated-acquisition task.

Pigeons acquired a different four-response chain each session by responding sequentially on three keys in the presence of four colors. The response chain was maintained by food presentation under a fixed-ratio schedule. Errors produced a brief timeout but did not reset the chain. When either morphine or naloxone was administered alone, the overall response rate decreased with increasing doses. The rate-decreasing effect was accompanied by an increase in percent errors with morphine but not with naloxone. Both effects of morphine were antagonized by doses of naloxone that were ineffective when given alone. The antagonism was selective in that naloxone (3 mg/kg) completely blocked the error-increasing effect but not the rate-decreasing effect of the higher doses of morphine. The view that naloxone is a specific narcotic antagonist was supported by the finding that naloxone failed to antagonize the rate-decreasing and error-increasing effects of d-amphetamine, pentobarbital, and phencyclidine.     

Choice between sequences of fixed-ratio schedules: effects of ratio values and probability of food delivery.

Pigeons were exposed to schedules of food delivery that consisted of two sequential fixed ratios. When alternative sequences provided two food deliveries per 50 responses, the schedule with the shorter initial fixed-ratio value was consistently preferred. Progressively reducing from 1.0 to .25 the probability of food delivery following completion of the second fixed ratio of the sequence with the shorter initial fixed ratio did not reduce preference for this sequence. Moreover, the sequence with the shorter initial fixed ratio also was preferred when the probability of food delivery following completion of the initial ratio in that sequence was progressively reduced from 1.0 to .5, although preference shifted to the alternative when the probability was reduced to 0. These findings suggest that the length of the initial fixed ratio was a primary determinant of choice. Subsequent manipulations demonstrated, however, that when the initial fixed ratios of the two alternatives were equal, changes in the ratio value and probability of food delivery following completion of the second fixed ratio lawfully affected choice.     

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.     

Choice with delayed and probabilistic reinforcers: effects of variability, time between trials, and conditioned reinforcers.

In a discrete-trials procedure with pigeons, a response on a green key led to a 4-s delay (during which green houselights were lit) and then a reinforcer might or might not be delivered. A response on a red key led to a delay of adjustable duration (during which red houselights were lit) and then a certain reinforcer. The delay was adjusted so as to estimate an indifference point--a duration for which the two alternatives were equally preferred. Once the green key was chosen, a subject had to continue to respond on the green key until a reinforcer was delivered. Each response on the green key, plus the 4-s delay that followed every response, was called one "link" of the green-key schedule. Subjects showed much greater preference for the green key when the number of links before reinforcement was variable (averaging four) than when it was fixed (always exactly four). These findings are consistent with the view that probabilistic reinforcers are analogous to reinforcers delivered after variable delays. When successive links were separated by 4-s or 8-s "interlink intervals" with white houselights, preference for the probabilistic alternative decreased somewhat for 2 subjects but was unaffected for the other 2 subjects. When the interlink intervals had the same green houselights that were present during the 4-s delays, preference for the green key decreased substantially for all subjects. These results provided mixed support for the view that preference for a probabilistic reinforcer is inversely related to the duration of conditioned reinforcers that precede the delivery of food.     

Fixed-ratio escape and avoidance-escape from naloxone in morphine-dependent monkeys: effects of naloxone dose and morphine pretreatment.

Lever pressing by rhesus monkeys was maintained by morphine injections during four equally spaced sessions each day. During other periods, lever pressing was maintained by timeout from a continuous naloxone infusion (escape), or by timeout from a stimulus that preceded naloxone injections, or termination of the injections (avoidance-escape). As naloxone dose increased in the escape procedure, response rate increased to a maximum and then decreased. In the avoidance-escape procedure, response rate generally increased as naloxone dose increased, but the changes in rate were small compared to the excape procedure. Substitution of saline for naloxone in the escape procedure led to a very low response rates within three sessions. In the avoidance-escape procedure, rate decrements produced by saline substitution appeared to be related to the behavioral history of the monkey. Previous escape experience led to more rapid decreases in responding when saline was introduced, whereas responding was maintained for 15 sessions in a monkey without prior escape conditioning. Morphine pretreatment produced comparable, dose-dependent decreases in response rates in both procedures. The rate-decreasing effects of morphine were exacerbated when no naloxone was delivered in the escape procedure.     

Variable-interval schedules of timeout from avoidance: effects of chlordiazepoxide, CGS 8216, morphine, and naltrexone.

Rats were trained on concurrent schedules in which pressing one lever postponed shock and pressing the other occasionally (variable-interval schedule) produced a 2-min timeout during which the shock-postponement schedule was suspended and its correlated stimuli were removed. These procedures provided a baseline for studying the effects of drugs on behavior maintained by different sources of negative reinforcement (shock avoidance and timeout from avoidance). Experiment 1 studied a benzodiazepine agonist, chlordiazepoxide, and antagonist, CGS 8216. Chlordiazepoxide (2.5-30 mg/kg) had little effect on avoidance responding except at higher doses, when it reduced responding. By comparison, responding on the timeout lever was increased in 5 of 6 rats. These effects were reversed by CGS 8216 (2.5-5 mg/kg) in the 2 rats tested, but CGS 8216 had no effect by itself. Experiment 2 studied an opiate agonist, morphine, and antagonist, naltrexone, with 3 rats. Morphine's (2.5-20 mg/kg) effects were opposite those of chlordiazepoxide: At doses that either increased or had no effect on avoidance responding, morphine depressed timeout responding. Naltrexone (5 mg/kg) reversed these actions but had no effect by itself.     

Variable-ratio schedules of timeout from avoidance: effects of d-amphetamine and morphine.

Rats were trained on concurrent schedules in which pressing one lever postponed shock and pressing the other lever produced periods of signaled timeout from avoidance on variable-ratio schedules. These procedures generated high rates of timeout-reinforced responding and provided a baseline for studying the effects of drugs on behavior maintained by different types of negative reinforcement (shock postponement vs. timeout). Morphine (2.5 to 10.0 mg/kg) reduced behavior maintained by timeout at doses that increased or had no effect on avoidance responding. In contrast, d-amphetamine (0.125 to 2.0 mg/kg) produced large increases in timeout responding at doses that had minimal effect on avoidance in rats trained on variable-interval and variable-ratio schedules. Thus, the event-dependent effects of morphine, observed in previous studies in which timeout responding was maintained at low rates by interval schedules, were replicated with high timeout rates maintained by variable-ratio schedules. The effects of d-amphetamine could also be described as "event dependent" because timeout responding was stimulated more than avoidance regardless of the maintenance schedule or baseline rate.     

Choice as a dependent measure in autoshaping: sensitivity to frequency and duration of food presentation.

Previous investigations have shown that rate, latency, and percentage of trials with at least one response are somewhat insensitive measures of the strength of autoshaped responding. In the present studies, these measures were contrasted with the allocation of responding during simultaneous choice tests, a measure of response strength frequently used in operant paradigms. In two experiments, nine pigeons were exposed to a forward pairing autoshaping procedure. Training sessions consisted of the successive presentation of three stimuli, each followed by food on either 100%, 50%, or 0% of the trials. Choice testing involved the simultaneous presentation of the three stimuli. In Experiment I, all pigeons consistently directed their initial choice responses and the majority of subsequent responses to the stimulus always followed by food, despite the fact that during training sessions the response rates of most birds were highest in the presence of the stimulus followed by food on 50% of the trials. In Experiment II, rate, latency, and percentage of trials with at least one response did not change appreciably as a function of duration of feeder presentations. However, choice responding was lawfully affected by duration of feeder presentations. These data suggest that choice is perhaps a more sensitive measure of the strength of autoshaped responding than other, more commonly employed, indices.     

Choice in a variable environment: effects of blackout duration and extinction between components

Pigeons were trained in a procedure in which sessions included seven four- or 10-reinforcer components, each providing a different reinforcer ratio that ranged from 27:1 to 1:27. The components were arranged in random order, and no signals differentiated the component reinforcer ratios. Each condition lasted 50 sessions, and the data from the last 35 sessions were analyzed. Previous results using 10-s blackouts between components showed some carryover of preference from one component to the next, and this effect was investigated in Experiment 1 by varying blackout duration from 1 s to 120 s. The amount of carryover decreased monotonically as the blackout duration was lengthened. Preference also decreased between reinforcers within components, suggesting that preference change during blackout might follow the same function as preference change between reinforcers. Experiment 2 was designed to measure preference change between components more directly and to relate this to preference change during blackout. In two conditions a 60-s blackout occurred between components, and in two other conditions a 60-s period of unsignaled extinction occurred between components. Preference during the extinction period progressively fell toward indifference, and the level of preference following extinction was much the same as that following blackout. Although these results are consistent with Davison and Baum's (2000) theory of the effects of reinforcers on local preference, other findings suggest that theory is incomplete: After a sequence of reinforcers from one alternative, some residual preference remained after 60 s of extinction or blackout, indicating the possibility of an additional longer term accumulation of reinforcer effects than originally suggested.     

Effects of delta 9-THC on marijuana smoking, dose choice, and verbal report of drug liking.

The effects of delta 9-tetrahydrocannabinol content of marijuana on cigarette smoking, dose choice, and verbal report of drug "liking" by adult males living in a residential laboratory were investigated. Marijuana cigarettes were available during programmed intervals while subjects were engaged in recreational activities. The tetrahydrocannabinol content of the cigarettes remained constant each day, but was changed across days. Subjects provided written ratings of drug liking at the end of each day. In the first study, placebo or active (2.3% delta 9-tetrahydrocannabinol) marijuana cigarettes were available for 1-, 2-, or 3-day intervals at varying times of day. The number of cigarettes smoked was unrelated to tetrahydrocannabinol content, although verbal reports of drug liking were consistently higher when marijuana cigarettes containing tetrahydrocannabinol were smoked. In a second study, a choice procedure, consisting of four 3-day blocks of 2 sample days and 1 choice day, was used. On sampling days, subjects smoked cigarettes varying in tetrahydrocannabinol content (0.0, 2.0, and 3.5%, w/w); on choice days they were allowed to choose between the two previously sampled doses. The number of cigarettes was not consistently related to tetrahydrocannabinol content. Ratings of drug liking were increased when marijuana cigarettes contained tetrahydrocannabinol, but ratings of marijuana containing 2.0% and 3.5% of the compound were similar. In contrast, subjects consistently chose the 3.5% dose over either the 0.0% or 2.0% dose. Dose choice was more sensitive to tetrahydrocannabinol content than either reports of drug liking or numbers of cigarettes smoked.     

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Choice with uncertain outcomes: conditioned reinforcement effects.

Pigeons responded on concurrent chains with equal initial- and terminal-link durations. In all conditions, the terminal links of one chain ended reliably in reinforcement; the terminal links on the alternative chain ended in either food or blackout. In Experiment 1, the terminal-link stimuli were correlated with (signaled) the outcome, and the durations of the initial and terminal links were varied across conditions. Preference did not vary systematically across conditions. In Experiment 2, terminal-link durations were varied under different stimulus conditions. The initial links were variable-interval 80-s schedules. Preference for the reliable alternative was generally higher in unsignaled than in signaled conditions. Preference increased with terminal-link durations only in the unsignaled conditions. There were no consistent differences between conditions with and without a common signal for reinforcement on the two chains. In the first series of conditions in Experiment 3, a single response was required in the initial links, and the stimulus conditions during 50-s terminal links were varied. Preference for the reliable outcome approached 1.0 in unsignaled conditions and was considerably lower (below .50 for 3 of 5 subjects) in signaled conditions. In a final series of signaled conditions with relatively long terminal links, preference varied with duration of the initial links. The results extend previous findings and are discussed in terms of the delay reduction signaled by terminal-link stimuli.     

Choice with delayed and probabilistic reinforcers: effects of prereinforcer and postreinforcer stimuli.

In Experiment 1, pigeons' pecks on a green key led to a 5-s delay with green houselights, and then food was delivered on 20% (or, in other conditions, 50%) of the trials. Pecks on a red key led to an adjusting delay with red houselights, and then food was delivered on every trial. The adjusting delay was used to estimate indifference points: delays at which the two alternatives were chosen about equally often. Varying the presence or absence of green houselights during the delays that preceded possible food deliveries had large effects on choice. In contrast, varying the presence of the green or red houselights in the intertrial intervals had no effects on choice. In Experiment 2, pecks on the green key led to delays of either 5 s or 30 s with green houselights, and then food was delivered on 20% of the trials. Varying the duration of the green houselights on nonreinforced trials had no effect on choice. The results suggest that the green houselights served as a conditioned reinforcer at some times but not at others, depending on whether or not there was a possibility that a primary reinforcer might be delivered. Given this interpretation of what constitutes a conditioned reinforcer, most of the results were consistent with the view that the strength of a conditioned reinforcer is inversely related to its duration.     

Effects of morphine, clonidine, and intensity change on electric-shock discrimination.

The effects of morphine, clonidine, and changes in stimulus intensity were examined in squirrel monkeys responding on one of two levers following brief presentations of one of two electric-shock intensities (0.1 and 0.5 mA). Responses were designated as correct or incorrect depending on which shock intensity had been presented and which lever was pressed. Morphine (0.42 to 1.80 mg/kg) and clonidine (0.075 to 0.18 mg/kg) decreased percentage correct responding. Morphine and clonidine also increased response latency and the number of shock presentations that were not followed by responses. Changes in shock intensity also decreased percentage correct responding but had no effect on response latency or on the number of shock presentations not followed by responses.     

Rate dependency, behavioral mechanisms, and behavioral pharmacology.

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.     

The long-term effects of naloxone,dibutyryl cyclic CMP,and chlorpromazine on aggression in mice monitored by an automated device

A device that records the squeaks of attacked mice, used in combination with a microcomputer, was evaluated as a means of monitoring fighting over extended periods. The influences of chlorpromazine, naloxone, and dibutyryl cyclic cytidine 3′5′ monophosphate were monitored for 23 hours. These drugs differed in their ability to decrease squeaking over this extended period. Naloxone, although it significantly decreased squeaking in the short-term, did not influence the 23-hour total. In contrast, dibutyryl cyclic cytidine 3′,5′ monophosphate proved to have a potent influence that resulted in a significant decrease in the total squeaking recorded over 23 hours.     

Food-deprivation level alters the effects of morphine on pigeons'' key pecking.

Four pigeons pecked response keys under a multiple fixed-ratio 30 fixed-interval 5-min schedule of food presentation. Components alternated separated by 15-s timeouts; each was presented six times. Pigeons were maintained at 70%, 85%, and greater than 90% of their free-feeding weights across experimental conditions. When response rates were stable, the effects of morphine (0.56 to 10.0 mg/kg) and saline were investigated. Morphine reduced response rates in a dose-dependent manner under the fixed-ratio schedule and at high doses under the fixed-interval schedule. In some cases, low doses of morphine increased rates under the fixed-interval schedule. When pigeons were less food deprived, reductions in pecking rates occurred at lower doses under both schedules for 3 of 4 birds compared to when they were more food deprived. When pigeons were more food deprived, low doses of morphine increased rates of pecking in the initial portions of fixed intervals by a greater magnitude. Thus, food-deprivation levels altered both the rate-decreasing and rate-increasing effects of morphine. These effects may share a common mechanism with increased locomotor activity produced by drugs and with increased drug self-administration under conditions of more severe food deprivation.     

Choice and foraging: the effects of accessibility on acceptability.

Pigeons responded in a successive-encounters choice procedure in which accessibility of the less profitable of two outcomes varied either in terms of probability of encounter or search time to encounter (keeping search time to the more profitable outcome constant). When the less profitable outcome was made more probable its acceptance became more likely. However, when search time to encounter the less profitable outcome was shortened, its acceptance became less likely. Both results are consistent with the delay-reduction hypothesis and with an optimality model developed for application to the successive-encounters choice procedure.     

Effects of methylphenidate and morphine on delay-discount functions obtained within sessions

Four rats responded under a "self-control" procedure designed to obtain delay-discount functions within sessions. Each session consisted of seven blocks, with seven trials within each block. Each block consisted of two initial forced-choice trials followed by five free-choice trials. On choice trials, the rats could press either of two retractable levers. A press on one lever was followed by presentation of a smaller reinforcer (a single dipper presentation of a sucrose solution); a press on the other lever was followed by presentation of a larger reinforcer (four consecutive dipper presentations). The delay associated with the smaller reinforcer always was 0 s, whereas the signaled delay associated with the larger reinforcer increased across blocks (from 0 to 50 s). Under these conditions, the percentage of choices of the larger reinforcer decreased across blocks, and relatively reliable delay-discount functions were obtained within sessions. Doses of methylphenidate (1.0 to 17.0 mg/kg) and morphine (0.3 to 17.0 mg/kg) were then administered prior to selected sessions. Typically, intermediate doses of methylphenidate shifted the discount functions to the right (increased choices of the larger reinforcer). For 2 of the rats, this effect was pronounced; for the other 2 rats, this effect occurred after the range of delays for the larger reinforcer was decreased (0 to 20 s). On the other hand, in most cases morphine produced a slight leftward shift in the discount function (decreased choices of the larger reinforcer). The present procedure appears to be a useful and efficient method to characterize drug effects on an entire delay-discount function. As with many procedures used to study self-control choices, however, sources of control other than reinforcement delay and amount may have been operating in the present study, and these sources must be considered when interpreting drug effects.