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Effects of delayed reinforcers on the behavior of an animal model of attention-deficit/hyperactivity disorder (ADHD).

Attention-deficit/hyperactivity disorder (ADHD), affecting 3-5% of grade-school children, is a behavioral disorder characterized by developmentally inappropriate levels of inattention, hyperactivity, and impulsivity. It has been suggested that the symptoms are caused by altered reinforcement and extinction processes, behaviorally described as an abnormally short and steep delay-of-reinforcement gradient in ADHD. The present study tested predictions from the suggested shortened and steepened delay gradient in ADHD in an animal model, the spontaneously hypertensive rats (SHRs). It was predicted that SHR responding during baseline would mainly consist of responses with short inter-response times, and that responding would be more rapidly reduced in the SHR than in the controls by the introduction of a time interval between the response and reinforcer delivery. Effects of a resetting delay of reinforcement procedure with water as the reinforcer were tested on two baseline reinforcement schedules: variable interval 30 s (VI 30 s) and conjoint variable interval 60 s differential reinforcement of high rate 1s (VI 60 s DRH 1 s). The results showed a higher rate of responses in the SHR than in the controls during baseline, mainly consisting of responses with short inter-response times. The statistical analyses showed that response rates decreased more rapidly as a function of reinforcer delay in the SHR than in the controls. The analyses of the estimates of the reinforcer decay parameter showed no strain differences during the VI 30 s schedule but showed a significant strain difference at the end, but not at the start, of the sessions during the VI 60 s DRH 1 s schedule. In general, the results support predictions from the suggested steepened delay gradient in SHR. However, the predictions were only partly confirmed by the analyses of the decay parameter.

Analysis of Variance↗

Operative mechanisms of noncontingent reinforcement at varying magnitudes and schedules.

In order to examine the mechanism(s) responsible for response reductions from noncontingent reinforcement (NCR), multiple magnitudes and densities of NCR were superimposed on a variable ratio (VR) 3 schedule of contingent reinforcement for the performance of an arbitrary manual response. Data were collected on responding that occurred during access to the reinforcer separately from responding that occurred between reinforcer access intervals (i.e.. when the participant did not have access to the reinforcer). Higher magnitudes and denser schedules of NCR produced greater reductions in responding than did lower magnitudes and leaner schedules. Within-session response patterns suggested that decrements in responding were primarily a function of the increased amount of reinforcer access time associated with higher magnitudes and denser schedules of NCR. That is, it appeared that the participant consumed reinforcers (regardless of whether they were delivered contingently or noncontingently) when they were available and responded for contingent reinforcers primarily when reinforcers were absent.

Adolescent↗

Use of a concurrent operants paradigm to evaluate positive reinforcers during treatment of food refusal.

The authors evaluated the responsiveness of 4 preschool-aged children to positive reinforcers within a concurrent operants paradigm during mealtimes. The children were presented with two identical, concurrently available sets of food. Each set differed in quantity and quality of positive reinforcement paired with acceptance of each bite of food or in the number of bites of food required to obtain positive reinforcement. Experiment 1 evaluated 1 child's responsiveness to positive reinforcement while permitting escape from bite offers. Experiment 2 evaluated 2 children's responsiveness to positive reinforcement when escape extinction occurred. Results from these experiments suggested that the children were responsive to positive reinforcers and chose more often the bites paired with the greater quantity and/or quality of reinforcement. Experiment 3 evaluated 1 child's responsiveness to positive reinforcement both without and with escape extinction. Results suggested that positive reinforcement affected choice behavior and that escape extinction affected amount of food consumed.

Behavior Therapy↗

The relation between response rates and reinforcement rates in a multiple schedule.

In a multiple schedule, exteroceptive stimuli change when the reinforcement schedule is changed. Each performance in a multiple schedule may be considered concurrent with other behavior. Accordingly, two variable-interval schedules of reinforcement were arranged in a multiple schedule, and a third, common variable-interval schedule was programmed concurrently with each of the first two. A quantitative statement was derived that relates as a ratio the response rates for the first two (multiple) variable-interval schedules. The value of the ratio depends on the rates of reinforcement provided by those schedules and the reinforcement rate provided by the common variable-interval schedule. The following implications of the expression were evaluated in an experiment with pigeons: (a) if the reinforcement rates for the multiple variable-interval schedules are equal, then the ratio of response rates is unity at all reinforcement rates of the common schedule; (b) if the reinforcement rates for the multiple schedules are unequal, then the ratio of response rates increases as the reinforcement rate provided by the common schedule increases; (c) the limit of the ratio is equal to the ratio of the reinforcement rates. Satisfactory confirmation was obtained for the first two implications, but the third was left in doubt.

Animals↗

Role of conditioned reinforcers in the initiation, maintenance and extinction of drug-seeking behavior.

The development of a secondary reinforcer as a result of associating a neutral stimulus (buzzer) with intravenous (IV) doses of morpine was studied in rats. Secondary reinforcement developed in the absence of physical dependence and followed the association of the stimulus with either response-contingent or non-contingent injections of morphine. Strength of the conditioned reinforcer, measured in terms of responding on a lever for the stimulus plus infusion of saline solution, was proportional to the unit dosage of morphine employed in pairings of buzzer and drug. When extinction of the lever-press response for IV morphine was conducted (by substituting saline for morphine solution) in the absence of the conditioned reinforcing stimulus, it was seen later that the stimulus could still elicit lever responses, until it too had been present for a sufficient interval of non-reinforced responding. Similarly, extinction of the response for morphine by blocking its action with naloxone in the absence of the stimulus did not eliminate the conditioned reinforcement. Another study showed that a passive, subcutaneous (SC) dose of morphine served to maintain lever-pressing on a contingency of buzzer plus saline infusion. Furthermore, the stimuli resulting from the presence of morphine (after a SC injection) were able to reinstate the lever-responding with only the buzzer-saline contingency when such responses had previously been extinguished. Moreover, it was shown that d-amphetamine could restore responding under the same conditions, and that morphine could also do so for rats in which the primary reinforcer had been d-amphetamine. It is suggested that animal data such as these show that procedures designed for the elimination of human drug-taking behavior must take into account secondary reinforcers as well as the primary reinforcer(s).

Amphetamine↗

Effects of lesions of the orbitofrontal cortex on sensitivity to delayed and probabilistic reinforcement.

RATIONALE: Lesions of the orbital prefrontal cortex (OPFC) can cause pathologically impulsive behaviour in humans. Inter-temporal choice behaviour (choice between reinforcers differing in size, delay and/or probability) has been proposed as a model of "impulsive choice" in animals. OBJECTIVE: The effect of lesions of the OPFC on rats' inter-temporal choice behaviour was examined in two experiments: (1) rats chose between a smaller immediate reinforcer and a larger delayed reinforcer; (2) rats chose between a smaller certain reinforcer and a larger probabilistic reinforcer. METHODS: Under halothane anaesthesia, rats received injections of the excitotoxin quinolinate into the OPFC (0.1 M, 0.5 microl, two injections in each hemisphere), or sham lesions (injections of vehicle). They were trained to press two levers (A and B) for food-pellet reinforcers in discrete-trials schedules. In free-choice trials, a press on A resulted in immediate delivery of one food pellet; a press on B resulted in delivery of two pellets, either following a delay ( d) (experiment 1), or with a probability ( p) <1 (experiment 2). The values of d and p were manipulated across phases of the experiments. The locations of the lesions were verified histologically at the end of the experiment. RESULTS: In experiment 1, both groups showed declining choice of lever B as a function of d. The lesioned rats showed significantly shorter indifference delays ( D50: the value of d corresponding to 50% choice of lever B) than the sham-lesioned rats. In experiment 2, both groups showed declining choice of lever B as a function of the odds against delivery of the two-pellet reinforcer, theta ( theta =[1/ p]-1). The lesioned rats showed lower indifference odds ( theta50: the value of theta corresponding to 50% choice of lever B) than the sham-lesioned rats. In both experiments, the lesioned rats showed extensive atrophy of the OPFC, with sparing of the dorsolateral prefrontal cortex. CONCLUSIONS: The results show that lesions of the OPFC can promote preference for the smaller and more immediate, and the smaller and more certain of two reinforcers. The results are consistent with two interpretations: the lesion may have altered (i) the rates of delay and odds discounting, and/or (ii) sensitivity to the ratio of the sizes of the two reinforcers.

Animals↗

Further studies of the reinforcing effects of benztropine analogs in rhesus monkeys.

RATIONALE: Several halogenated analogs of benztropine (BZT) have previously been characterized as potent DA uptake inhibitors with behavioral profiles that indicate diminished psychomotor stimulant effects relative to cocaine. In a previous study using a fixed-ratio 10 schedule, two chloro-analogs (3'-Cl-BZT and 4'-Cl-BZT) maintained i.v. self-administration in monkeys but appeared to be weak positive reinforcers. OBJECTIVES: The present experiments were designed to test the hypothesis that 3'-Cl-BZT and 4'-Cl-BZT are relatively weak reinforcers by evaluating reinforcing effects under increased response requirements. To examine further the effect of this halogen substitution on self-administration, 3',4"-diCl-BZT was also evaluated for reinforcing effects. METHODS: Four rhesus monkeys self-administered cocaine (0.03 mg/kg per injection, i.v.) under a fixed-ratio 25 (FR25) schedule until stable responding was established. Saline, various doses of cocaine (0.003-0.2 mg/kg per injection), the BZT analogs (0.012-0.2 mg/kg per injection), GBR 12909 (0.012-0.2 mg/kg per injection), and compounds with known reinforcing effects (d-amphetamine, morphine, pentobarbital, ketamine) were then made available for self-administration. Various doses (0.01-0.3 mg/kg per injection) of the compounds that maintained self-administration under the FR schedule were then substituted for cocaine (0.1 mg/kg per injection) under progressive-ratio (PR) schedules. RESULTS: Reinforcing effects were evident under the FR schedule for 3'-Cl-BZT, 4'-Cl-BZT, GBR 12909, and the control compounds, but not by 3',4"-diCl-BZT. Results with the PR suggested that the rank order of these compounds for their effectiveness as reinforcers was cocaine > GBR 12909 > 3'-Cl-BZT = 4'-Cl-BZT >> 3',4"-diCl-BZT. CONCLUSIONS: This study confirms and extends previous results suggesting that compounds with high DAT affinity can have strong, moderate, weak, or no effectiveness as reinforcers. The mechanisms that may underlie this variation in reinforcing effectiveness of these DAT ligands remain to be established.

Animals↗

Effect of central 5-hydroxytryptamine depletion on changeover behaviour in concurrent schedules of reinforcement.

RATIONALE: Previous experiments have shown that rats whose 5-hydroxytryptaminergic (5-HTergic) pathways have been destroyed exhibit higher rates of switching between response alternatives on various temporal differentiation schedules. OBJECTIVE: This paper reports two experiments investigating the effect of central 5-HT depletion on switching between concurrent schedules of reinforcement which do not entail temporal differentiation of behaviour. METHODS: Rats received injections of 5,7-dihydroxytryptamine into the dorsal and median raphe nuclei or sham lesions. They were trained to press levers for sucrose reinforcement. In experiment 1, the rats were exposed to concurrent pairs of variable-time (VT) schedules specifying equal inter-reinforcement intervals; responses on a single "changeover lever" alternated between the two VT schedules. In experiment 2, the rats were exposed to concurrent pairs of variable-interval (VI) schedules specifying equal inter-reinforcement intervals; responses on one lever ("VI lever") earned reinforcers, while responses on the other lever ("changeover lever") alternated between the two VI schedules. RESULTS: In experiment 1, both groups showed longer "dwell-times" (intervals between successive changeover responses) when a reinforcer was delivered in the "dwell" than when no reinforcer was delivered ("win-stay" effect). The lesioned rats showed higher rates of changeover responding and shorter dwell-times (with and without reinforcer delivery) than the sham-lesioned group. In experiment 2, the rate of responding on the VI lever did not differ significantly between the two groups; however, the lesioned rats showed higher rates of changeover responding, shorter dwell-times (with and without reinforcer delivery) and smaller numbers of inter-changeover responses on the VI lever than the sham-lesioned group. In both experiments, the levels of 5-HT and 5-hydroxyindoleacetic acid were reduced in the brains of the lesioned rats, but the levels of noradrenaline and dopamine were not altered. CONCLUSIONS: These results provide further evidence for the involvement of the ascending 5-HTergic pathways in behavioural "switching", and indicate that this is not restricted to temporal differentiation schedules.

Animals↗

Amphetamine and the multitrial partial reinforcement extinction effect (PREE) in an operant chamber: procedural modifications that lead to an attenuation of the PREE.

The partial reinforcement extinction effect (PREE) consists of the fact that animals receiving partial reinforcement (PRF) exhibit higher resistance to extinction than animals receiving continuous reinforcement (CRF). In previous studies, we found that amphetamine (AMPH) did not affect resistance to extinction of PRF animals trained with a multitrial procedure, but abolished resistance to extinction of PRF animals trained with a 1 trial/day procedure. Based on theoretical distinctions regarding the processes underlying the development of increased resistance to extinction at short and long intertrial intervals, we suggested that AMPH disrupts the formation of a context-mediated association between stimuli associated with nonreinforcement and subsequent reinforcement. To examine further this possibility, we designed conditions in a multitrial PRF procedure that do not allow a direct association between stimuli associated with nonreinforcement and reinforcement, and thus promote a context-mediated association between them. Two experiments were conducted in an operant chamber. In experiment 1, instead of the conventional 50% schedule of reinforcement throughout PRF training, days of 33% schedule of reinforcement were interspersed with days of continuous reinforcement; in experiment 2, a block (5 days) of 50% PRF schedule was alternated with a block (5 days) of CRF training, given either prior to or following PRF. In experiment 1, interspersing days of CRF training with days of 33% reinforcement schedule led to an attenuation of the PREE in AMPH-treated animals. In experiment 2, control animals that received CRF training either prior to or following PRF training exhibited a PREE similar to animals trained on PRF alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Amphetamine↗

Nucleus accumbens cell firing during goal-directed behaviors for cocaine vs. 'natural' reinforcement.

Numerous investigations indicate that the nucleus accumbens (Acb) is an important neural substrate mediating the reinforcing properties of 'natural' rewards (food or water) as well as abused substances. Here, our electrophysiological studies that examined Acb cell firing within seconds of lever press responding for intravenous cocaine vs. water or food reinforcement in rats are reviewed. Initial investigations revealed that a subset of Acb neurons exhibits four types of firing patterns within seconds of the reinforced response for intravenous cocaine during self-administration sessions. Three of those four cell types were also observed during water reinforcement sessions. In a subsequent study, the activity of the same Acb neurons was examined in rats responding on multiple schedules for either two distinct 'natural' reinforcers (water and food), or one of those 'natural' reinforcers and the intravenous self-administration of cocaine. The results showed that the majority of neurons tested exhibited similar, overlapping neuronal firing patterns across the two 'natural' reinforcer conditions. In contrast, the majority of neurons examined displayed differential, nonoverlapping firing patterns relative to operant responding for water (or food) vs. cocaine reinforcement. Additional studies that examined the role of associative factors on Acb cell firing during cocaine self-administration sessions are reviewed. Collectively, these findings illustrate the dynamic nature of Acb cell firing in behaving animals, and provide insight into how Acb neurons process information about goal-directed behaviors for 'natural' reinforcers vs. abused substances.

Animals↗

Effect of partial reinforcement on tolerance to morphine-induced analgesia and weight loss in the rat.

The effect of partial reinforcement on the development of tolerance to morphine-induced analgesia and weight loss was examined. Groups of rats were presented a distinctive set of environmental cues on several occasions. For one group of rats, morphine (40 mg/kg) was injected each time the cues were presented (morphine--continuous reinforcement). For a second group of rats, morphine was injected only following one of every four cue presentations (morphine--partial reinforcement). Two additional groups were injected with only saline, one on the continuous reinforcement schedule and one on the partial reinforcement schedule. Results demonstrated less tolerance to morphine in the partially reinforced morphine-injected rats than in continuously reinforced morphine-injected rats. Unlike other demonstrations of a tolerance-retarding effect of partial reinforcement, the present results could not have resulted from nonassociative factors related to differential novelty, stress, or practice. Clinical implications for the tolerance-retarding effect of partial reinforcement are discussed.

Animals↗

Relations between Pavlovian-instrumental transfer and reinforcer devaluation.

Relations between posttraining reinforcer devaluation and Pavlovian-instrumental transfer were examined in 2 experiments. When a single reinforcer was used, extended training of the instrumental response increased transfer but reduced devaluation effects. When multiple instrumental reinforcers were used, both reinforcer-specific transfer and devaluation effects were less influenced by the amount of instrumental training. Finally, although reinforcer devaluation decreased both Pavlovian conditioned responses and baseline instrumental responding, it had no effect on either single-reinforcer or reinforcer-specific transfer. These results indicate that transfer and reinforcer devaluation can reflect different aspects of associative learning and that the nature of associative learning can be influenced by parameters such as the amount of training and the use of multiple reinforcers.

Analysis of Variance↗

Sensitivity of nicotine-containing and de-nicotinized cigarette consumption to alternative non-drug reinforcement: a behavioral economic analysis.

A previous report from our laboratory showed similar measures of reinforcing efficacy for nicotine-containing and de-nicotinized cigarettes when each cigarette type was presented alone. The present experiment further compared the reinforcing efficacy of nicotine-containing and de-nicotinized cigarettes by assessing the effects of alternative non-drug reinforcement on self-administration of both cigarette types. Eight human subjects responded on a progressive-ratio schedule in which the number of plunger pulls required for standardized cigarette puffs increased across sessions. Responding for the two types of cigarette was examined when each was available alone and when the concurrent opportunity to earn money was available. Consumption of nicotine-containing and de-nicotinized cigarettes was decreased by both increases in price and by the concurrent availability of money. The two cigarettes types did not differ in their sensitivity to price or alternative non-drug reinforcement. These results replicate our previous report of similar measures of reinforcing efficacy for the two cigarette types when each was presented alone, and extend our previous findings to a choice situation involving an alternative non-drug reinforcer. These data suggest the importance of further examination of non-pharmacological variables in the maintenance of drug taking and the sensitivity of drug taking to alternative non-drug sources of reinforcement. Factors potentially contributing to the maintenance of smoking the de-nicotinized cigarettes (i.e. conditioned reinforcement, primary reinforcement by respiratory stimulation, instructional control, demand characteristics) are also discussed.

Adult↗

Primary reinforcing effects of nicotine are triggered from multiple regions both inside and outside the ventral tegmental area.

Nicotine is thought to be the key substance responsible for tobacco-smoking habits and appears to trigger reinforcement via the ventral tegmental area (VTA). Recently, multiple anatomical substrates for drug reinforcement have been identified in the vicinity of the ventral midbrain. In addition to the posterior portion of the VTA, the central linear nucleus raphé and the supramammillary nucleus of the posterior hypothalamus mediate drug reinforcement. Using intracranial self-administration procedures, we examined whether these regions mediate the reinforcing effects of nicotine. Rats learned to lever press for self-administration of nicotine into the posterior VTA, central linear nucleus, and supramammillary nucleus, suggesting a reinforcing action of nicotine in these regions. The rats did not self-administer nicotine into surrounding regions including the anterior VTA, substantia nigra, the region just dorsal to the posterior VTA, interpeduncular nucleus, or medial mammillary nucleus. The reinforcing effects of nicotine into the three brain regions were further confirmed by a two-lever discrimination procedure, in which rats learned to selectively respond between active and inactive levers. The reinforcing effects of nicotine administration into the posterior VTA, central linear nucleus, and supramammillary nucleus were blocked by coadministration of the nicotine receptor antagonist mecamylamine. The reinforcing effects of nicotine into the posterior VTA or central linear nucleus were attenuated by coadministration of the D2 receptor agonist quinpirole. These findings demonstrate that nicotine reinforcement involves multiple regions both inside and outside the VTA.

Animals↗

Sensory extinction and sensory reinforcement principles for programming multiple adaptive behavior change.

The role of sensory reinforcement was examined in programming multiple treatment gains in self-stimulation and spontaneous play for developmentally disabled children. Two phases were planned. First, we attempted to identify reinforcers maintaining self-stimulation. Sensory Extinction procedures were implemented in which auditory, proprioceptive, or visual sensory consequences of self-stimulatory behavior were systematically removed and reintroduced in a reversal design. When self-stimulation was decreased or eliminated as a result of removing one of these sensory consequences, the functional sensory consequence was designated as a child's preferred sensory reinforcer. In Phase 2, we assessed whether children would play selectively with toys producing the preferred kind of sensory stimulation. The results showed the following. (1) Self-stimulatory behavior was found to be maintained by sensory reinforcement. When the sensory reinforcer was removed, self-stimulation extinguished. (2) The sensory reinforcers identified for self-stimulatory behavior also served as reinforcers for new, appropriate toy play. (3) The multiple treatment gains observed appeared to be relatively durable in the absence of external reinforcers for play or restraints on self-stimulation. These results illustrate one instance in which multiple behavior change may be programmed in a predictable, lawful fashion by using "natural communities of sensory reinforcement."

Autistic Disorder↗

The conditioning of textual responses using "extrinsic" reinforcers.

Six 4-year-old Ss were presented with a textual program consisting of 26 words arranged so the word stimuli were gradually combined into sentences and then short "stories." Three Ss were given the No-Reinforcement condition first, and only social reinforcers were presented. They were switched to the Reinforcement condition as soon as they requested discontinuance of the activity. The other three Ss were given Reinforcement-No Reinforcement-Reinforcement treatments. The No-Reinforcement treatment in this case lasted until S requested discontinuance of the activity. The reinforcers were mixed edibles and trinkets, as well as tokens backed up by small plastic toys on a 1:24 ratio. The unit of response was the number of new texts acquired as a result of each of the 45-min experimental sessions. It was demonstrated that the program, procedure, and reinforcement conditions produced curves which are analogous to those produced in common operant-conditioning procedures. The results indicate that other operant principles may be studied in this significant area of human behavior, with important practical consequences.

Conditioning, Operant↗

Effects of delayed reinforcement on infant vocalization rate.

Three previous studies have failed to demonstrate conditioning in infants using a 3-s delay of reinforcement. The effects of a delayed reinforcement schedule on vocalization rates therefore were explored in a single-subject repeated-reversal experimental design for 3 4- to 6-month-old normally developing infants. Each infant received delayed social reinforcement from his or her parent for vocalizing. The comparison condition was a schedule of differential reinforcement of behavior other than vocalizations to control for elicitation by social stimulation. An operant level of infant vocalizations was the initial condition, after which the differential reinforcement schedule was implemented in an across-subjects multiple baseline design. Infants' vocalization rates increased above levels measured during differential reinforcement following onset of the delayed reinforcement condition. Also, vocalization rates decreased during differential reinforcement compared to operant levels. The successful use of delayed reinforcement schedules with infants in this study, as opposed to others, is discussed in terms of procedural differences among them.

Arousal↗

Studies of wheel-running reinforcement: parameters of Herrnstein's (1970) response-strength equation vary with schedule order.

Six male Wistar rats were exposed to different orders of reinforcement schedules to investigate if estimates from Herrnstein's (1970) single-operant matching law equation would vary systematically with schedule order. Reinforcement schedules were arranged in orders of increasing and decreasing reinforcement rate. Subsequently, all rats were exposed to a single reinforcement schedule within a session to determine within-session changes in responding. For each condition, the operant was lever pressing and the reinforcing consequence was the opportunity to run for 15 s. Estimates of k and R(O) were higher when reinforcement schedules were arranged in order of increasing reinforcement rate. Within a session on a single reinforcement schedule, response rates increased between the beginning and the end of a session. A positive correlation between the difference in parameters between schedule orders and the difference in response rates within a session suggests that the within-session change in response rates may be related to the difference in the asymptotes. These results call into question the validity of parameter estimates from Herrnstein's (1970) equation when reinforcer efficacy changes within a session.

Animals↗