Operant Schedule Research Articles

A microdialysis study of nucleus accumbens core and shell dopamine during operant responding in the rat

This investigation examined dopamine release and metabolism in nucleus accumbens core and shell during three operant tasks in the rat. Rats were trained to lever press on a fixed-ratio 5, variable-interval 30 s, or a tandem variable interval 30/fixed-ratio 5 schedules; these three schedules were chosen because they generate a wide range of response and reinforcement rates. After several weeks of training, dialysis probes were implanted into nucleus accumbens core or shell subregions. A single 30 min behavioural session was conducted during the dialysis test session. Rats lever pressing on each of the three operant schedules showed a significant increase in extracellular dopamine relative to the food-deprived control group during the behavioural session. In addition, increases in dopamine in nucleus accumbens shell were found to be significantly greater than in the core during the lever pressing period. Across all three schedules, extracellular dopamine in the nucleus accumbens was significantly correlated with the number of lever presses performed, but was not correlated with the number of food pellets delivered. Analysis of covariance, which used amount of food consumed as the covariate, showed an overall group difference, indicating that dopamine levels increased in lever pressing animals even if one corrected for the amount of food consumed. These results indicate that dopamine release was more responsive in the nucleus accumbens shell than in the core during operant responding, and that increases in extracellular dopamine in nucleus accumbens are related to response rate rather than reinforcement magnitude.

The effects of the novel benzodiazepine receptor inverse agonist Ru 34000 on ethanol-maintained behaviors

Ru 34000 [5-ethyl-7-methoxy-imidazo (1,2-a) pyrimidin-2-yl cyclopropyl methanone] is a novel imidazopyrimidine benzodiazepine inverse agonist that exhibits low affinity for central benzodiazepine receptors ( K i≈0.98 μM). The present study examined the in vivo actions of Ru 34000 (0.5–5 mg/kg) following intraperitoneal (i.p.), subcutaneous (s.c), oral (p.o.), and intraventral tegmental administration in alcohol-preferring (P) rats trained under a concurrent operant schedule (FR4–FR4) for ethanol (10% v/v) and a palatable saccharin (0.025% or 0.75% w/v) reinforcer. Ru 34000 (i.p., s.c., p.o.) markedly reduced ethanol responding by 28–96% of control levels without affecting saccharin responding, except for the highest dose level. Clear dose-dependent suppressant effects were observed with all routes of administration on ethanol responding. Flumazenil [ethyl-8-fluro-5, 6-dihydro-5-methyl-6-4 H-imidazo [1,5-a]-[1,4]-benzodiazepine-3-carboxylate] (6 mg/kg; i.p.), a benzodiazepine receptor antagonist reversed the Ru 34000-reduction of ethanol responding, suggesting that the effects were mediated at the benzodiazepine receptor. Bilateral microinjections of Ru 34000 (50, 100, 200 ng) into the ventral tegmental area dose-dependently reduced ethanol responding by as much as 97% of control levels. The results suggest that the in vivo actions of Ru 34000 are determined not only by its binding affinity, but also by its bioavailability at active benzodiazepine sites and route of drug administration. Low affinity imidazopyrimidines may be useful pharmacological probes to further understand the role of the GABA A-benzodiazepine receptor complex in ethanol motivated behaviors.

Ethanol’s Effects on Operant Responding: Differentiating Reinforcement Efficacy and Motor Performance

PETRY, N. M. Ethanol’s effects on operant responding: Differentiating reinforcement efficacy and motor performance. Physiol Behav 64(1) 117–122, 1998. The purpose of this study was to examine the effects of ethanol on operant responding in rats. Drugs may affect response rates by several mechanisms, including altering motor performance or sensitivity to reinforcement. These two processes can be dissociated by applying a quantitative model of reinforced responding the response–strength equation, to response rates obtained during multiple variable-interval (VI) schedules of reinforcement. This equation has two fitted parameters. One ( k) is thought to measure changes in motor performance, and the other ( R e) is thought to measure changes in reinforcement efficacy. In experimental sessions, rats earned sucrose reinforcement on a seven-component multiple VI operant schedule. The average intervals varied from 108 to 3 s and provided reinforcement rates from 30 to 1200/h. Following stable baseline performance, rats were injected intraperitoneally prior to sessions with different doses of ethanol: 0.0, 0.3, 0.6, and 0.9 g/kg. Low to moderate doses of ethanol (0.3 and 0.6 g/kg) significantly decreased response rates on several of the VI schedules but did not alter either of the fitted parameters, suggesting that these doses of ethanol did not affect motor performance or sensitivity to reinforcement. The 0.9 g/kg dose decreased responding maintained by many of the VI schedules and significantly increased the R e parameter, suggesting that the sucrose became relatively less efficacious in ethanol compared to vehicle sessions. This relatively high dose of ethanol, however, did not alter responding maintained by the richest reinforcement schedule, and it did not affect motor performance as defined by the k parameter. These results suggest that, within this paradigm, ethanol affects motivation to respond rather than ability to respond.

Coronary vasoreactivity to ergonovine after angioplasty

A reduced behavioral sensitivity to drugs acting on central GABAergic, serotonergic, opioid and cholinergic systems has previously been identified in predominantly male malnourished animals. The present study sought to compare the effects of the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 on responding maintained by a differential reinforcement of low rates (DRL-18s) operant schedule in two groups of rats with different prenatal nutritional histories (well-nourished and protein restricted). The schedule required that the rats space their responses at least 18 s apart in order to obtain food reinforcement (timing behavior). After training to a stable high proficiency, MK-801 was administered to female rats (Experiment 1) at doses of 0 (saline), 0.004, 0.008, 0.016, 0.024 or 0.032 mg/kg (doses expressed as the free-base). MK-801 produced dose-dependent decreases in the percentage efficiency of responding and the number of rewarded responses, with dose-dependent increases in the number of responses emitted. Prenatal malnutrition significantly shifted the inter-response time (IRT) curve to the left, relative to that of the well-nourished controls, leading to a significantly lower efficiency and a lower number of reinforcers, at an MK-801 dose of 0.016 mg/kg. In Experiment 2, the effect of MK-801 on DRL performance was compared between male and female rats after prenatal malnutrition. In general, females proved more sensitive to MK-801 than males. Consistent with Experiment 1, a significantly greater drug impairment was observed in prenatally malnourished females compared with well-nourished females, albeit at a slightly higher dose (0.032 mg/kg). Prenatal malnutrition did not alter the drug response in male rats. These findings suggest that the behavioral response to NMDA blockade is augmented in adult female, but not male, rats after prenatal malnutrition.

The novel benzodiazepine inverse agonist RO19-4603 antagonizes ethanol motivated behaviors: neuropharmacological studies

The novel imidazothienodiazepine inverse agonist RO19-4603 has been reported to attenuate EtOH intake in home cage drinking tests for at least 24 h post-drug administration after systemic administration. In the present study, selectively bred alcohol-preferring (P) rats were trained under a concurrent (FR4–FR4) operant schedule to press one lever for EtOH (10% v/v) and another lever for saccharin (0.05% or 0.75% g/v), then dose-response and timecourse effects of RO19-4603 were evaluated. Systemic RO19-4603 injections (0.0045–0.3 mg/kg; i.p.) profoundly reduced EtOH responding by as much as 97% of vehicle control on day 1. No effects were seen on saccharin responding except with the highest dose level (0.3 mg/kg). In a second experiment, microinjections of RO19-4603 (2–100 ng) directly into the nucleus accumbens (NA) suppressed EtOH responding on day 1 by as much as 53% of control: Control injections dorsal to the NA or ventral tegmental area did not significantly alter EtOH or saccharin responding. On day 2, rats in both experiments received no RO19-4603 treatments; however, all 7 of the i.p. doses, and all 3 of the intra-NA infusions continued to significantly suppress EtOH responding by 43–85% of vehicle control levels. In addition, i.p. injections of RO19-4603 produced a dose-dependent decrease in the slope of the cumulative record for EtOH responding, while concomitantly producing a dose-dependent increase in the slope for saccharin responding. RO19-4603's actions appear to be mediated via recognition sites at GABA A-BDZ receptors which regulate EtOH reinforcement, and not via mechanisms regulating ingestive behaviors. Based on recent in situ hybridization studies in our laboratory, we hypothesize that occupation of α 4 containing GABA A diazepam insensitive (DI) receptors in the NA, may mediate in part, the RO19-4603 suppression of EtOH responding in EtOH-seeking P rats.

Primidone-induced embryolethality and DRL deficits in surviving offspring.

Pregnant Sprague-Dawley rats were administered primidone (PRM) by oral gavage on gestation days 8-20 in doses of 0 or 120 mg/kg. This dose did not produce body weight differences in the dams during the dosing period nor were there differences in the birth weights of the offspring. PRM was embryolethal with only 43% of drug-treated dams maintaining their pregnancies, whereas 100% of the pregnant controls produced offspring. An analysis of resorption sites in PRM-treated dams that did not deliver showed a nearly identical number of implantation sites (12.6) compared to the litter size of controls (12.8) that delivered pups. There were no overall differences in exploratory activity levels between PRM-treated and control animals. However, in the PRM-treated females there was an absence of the sexually dimorphic increase in activity seen in control females when compared to control males. The PRM-treated males showed an impairment in the acquisition of a DRL-20 (differential reinforcement of low rates) operant schedule over a 9-week acquisition period. There were no differences in the total response rates between the groups, suggesting that this is a specific learning deficit and not a performance deficit. The results of these experiments provide evidence that prenatal PRM exposure can be embryolethal and also impair behavior in the surviving rat offspring.

Neuropeptide Y-induced operant responding for sucrose is not mediated by dopamine

Neuropeptide Y (NPY) induces feeding in previously satiated animals after injection into the hypothalamus, especially the perifornical region (PFH). NPY also appears to have rewarding properties as evidenced by its ability to produce a conditioned place preference following injection into the nucleus accumbens (N.Acc), an effect ostensibly mediated by mesolimbic dopamine (DA). Since the progressive-ratio (PR) operant schedule has also been used to assess an organism’s motivation to respond for rewarding stimuli, we tested the possibility that NPY increases PR responding for sucrose pellets. Adult male rats were injected with NPY (0–235 pmol) bilaterally through cannulae aimed to terminate in the PFH. This produced a dose-dependent increase in the total number of responses made and the number of reinforcers earned. The DA receptor blocker, α-flupenthixol (FLU)(0–0.2 mg/kg intraperitoneally), attenuated both NPY(156 pmol)-induced and drug-free PR responding while having no effect on NPY(156 pmol)-induced free-feeding. FLU injected directly into the N.Acc (0–5 μg) also failed to reduce sucrose free-feeding. These results suggest that distinct reward mechanisms are activated during PFH NPY-induced feeding vs. PR responding, since FLU disrupted the latter but not the former.

Dynamic query operator scheduling for wide-area remote access

Distributed databases operating over wide-area networks such as the Internet, must deal with the unpredictable nature of the performance of communication. The response times of accessing remote sources can vary widely due to network congestion, link failure, and other problems. In such an unpredictable environment, the traditional iterator-based query execution model performs poorly. We have developed a class of methods, called query scrambling, for dealing explicitly with the problem of unpredictable response times. Query scrambling dynamically modifies query execution plans on-the-fly in reaction to unexpected delays in data access. In this paper we focus on the dynamic scheduling of query operators in the context of query scrambling. We explore various choices for dynamic scheduling and examine, through a detailed simulation, the effects of these choices. Our experimental environment considers pipelined and non-pipelined join processing in a client with multiple remote data sources and delayed or possibly bursty arrivals of data. Our performance results show that scrambling rescheduling is effective in hiding the impact of delays on query response time for a number of different delay scenarios.

Acute Amino Acid Loads That Deplete Brain Serotonin Fail to Alter Behavior

Acute depletion of brain serotonin (5-HT) can be induced in both rats and humans by giving an amino acid load deficient in tryptophan (TRY). Because this treatment is relatively easy to administer and short-acting, it seems well suited for studying mood and/or behavioral changes linked to aberrant 5-HT functioning in humans. To investigate the ability of a TRY-deficient amino acid load to induce behavioral changes in animals, this study measured performance on an operant schedule of differential reinforcement of low rates of responding (DRL), locomotor activity in both novel and familiar environments, and paw-lick latencies on a hot-plate. All of these measures have been found previously to be altered by impairments of the brain 5-HT system. Adult male Sprague–Dawley rats were administered by gavage an amino acid load lacking TRY, an amino acid load containing TRY, or distilled water. Three hours later, behavioral tests were conducted. Although 5-HT levels were decreased in the hippocampus (−23.3%) and 5-hydroxyindoleacetic acid (5-HIAA) levels were decreased in the striatum (−35.1%) and hippocampus (−38.5%), there were no effects of the TRY-deficient load on any of the behavioral tests. Because reliable mood-altering effects have been reported in human subjects using this method, their behavioral counterparts may be too subtle to observe in animals. Alternatively, effects observed in humans may reflect nonserotonergically mediated consequences of such tryptophan deficient amino acid loads and/or preexisting abnormalities of 5-HT or other systems in such people.

An Application of Discrete-Event Simulation for Batch-Process Chemical-Plant Design

Operating a batch-processing chemical-plant efficiently is difficult. Chemical processes require specialized equipment that is sensitive to precise operating conditions and subject to strict quality conformance. Chemical formulations having unique attributes require the simultaneous use of multiple resources to process and move products through the plant. One of our clients used a generic simulation model we developed to help design and operate a multimillion-dollar batch-process chemical facility. Our client used the model to evaluate the impact of many complex issues—such as scheduling policy, inventory policy, resource sizing and configuration, operator schedules, and processing capability—for a proposed process facility. The client used the model to identify throughput issues related to new plant designs and to evaluate proposed improvements prior to implementation, thus saving considerable cost and time.

Agent-based airline scheduling

The development of an airline schedule can be defined as the art of developing system-wide flight patterns that deliver optimum service to the public in terms of quantity as well as quality. The development of the schedule is market driven with maintenance and crew requirements as constraints. This paper deals with an integrated agent-based approach for the airline scheduling problem. A bidding protocol is used to generate a market based schedule. FIFO and genetic algorithms are used to develop a crew schedule. An expert system combined with the Q-learning algorithm assist operational schedulers in resolving operational conflicts such as delays.

Investigations into the nature of a 7-OH-DPAT discriminative cue: Comparison with d-amphetamine

In the present study, separate squads of rats were trained to discriminate either the dopamine D 3 receptor preferring ligand 7-hydroxy-2-(di- N-propylamino)-tetralin (7-OH-DPAT) (0.03 mg/kg) from saline, or d-amphetamine (0.3 mg/kg) from saline using a standard operant schedule (FR10 schedule reinforcement). Following stable acquisition of responding, tests of generalisation and antagonism were conducted. A number of dopamine agonists having high dopamine D 2-like receptor (D 2, D 3 or D 4) affinity generalised to the 7-OH-DPAT, but not amphetamine, cue. The dopamine D 1/5 receptor agonist SKF38393 showed no generalisation to either drug cue. Subsequent correlational analysis suggested that this effect was most likely mediated through the dopamine D 3 receptor. The dopamine D 2/3 receptor antagonist raclopride significantly attenuated both cues. The failure of these drugs to generalise to amphetamine, suggest that there is little involvement of the dopamine D 3 receptor subtype in mediating its discriminative stimulus properties.

Surgical informatics is a useful management tool

Background Management of surgery in the largest health care system in the country depends upon readily available and valid data. Use of an administrative data base had not fulfilled these requirements. An information program based upon the computerized operating room log and scheduling program presented a possible remedy. Methods Data elements previously appearing in the computerized operating room log were expanded to include outcomes. Reports essential to the surgical management of VA surgery were developed through an advisory panel. Necessary changes were added to the surgical computer program and computers installed in each operating room throughout the system. Results The work load information to manage a surgical service was determined to include the total number of operations performed, both major and minor, and a description of the patient population including the American Society of Anesthesiologists (ASA) classification. The breakdown into the individual surgical specialties, information regarding index operations, extent of resident supervision, and incidence of postoperative occurrences completed the required information. Conclusions The information provided by this report is an example of the importance of the use of surgical informatics in the management of VA surgery. The ability to obtain valid information for analysis and dissemination is a direct result of the computer-generated information taken directly from the surgical log of each of the 126 VA Medical Centers.

Operant schedule transformations and human behavioral momentum

Behavioral momentum, which can be defined as the persistence of behavior under altered environmental contingencies, is derived from Newtonian physics and operant psychology, and has relevance to behavior therapy in terms of shaping strong behaviors and ensuring effective relapse prevention strategies. The present study investigated whether changing operant schedule contingencies affects how humans respond to different stimuli when reinforcement density is systematically manipulated. Fifteen subjects participated in a computer study, in which each of two keys in a baseline condition was associated with the same schedule of reinforcement, multiple variable interval schedules, the only difference being that one reinforcer was ten times larger than the other. After six sessions, the contingency schedule changed to either an extinction condition, a variable time schedule, or a changed variable interval schedule to assess how subjects' responses persisted when reinforcement contingencies were systematically changed. Results of this study were found to be consistent with the general predictions of behavioral momentum. Subjects not only biased responding in favor of the more densely reinforcing key, but when contingencies changed, subjects showed continued biased responding. Implications for behavioral momentum for behavior modification and behavior therapy are discussed, and it is concluded that behavioral momentum has significant implications for designing new and comprehensive behavior change programs.

Improving telemarketers' performance in the short-run using operant concepts

Telemarketers working a day (N=7) and evening shift (N=7) failed to achieve required rates of calls completed when they worked under a numerical quota system (pre-intervention baseline period). The existing system was analyzed using operant terms and concepts. Then, an operant-based system of individual rewards contingent on meeting a group quota (intervention or treatment system) of one week duration was operationalized during weeks four and five respectively for the day and evening shifts in multiple baseline fashion across the two groups. The operant- based incentive system produced practically and statistically reliable performance increases among day and evening shift telemarketers. Results are discussed in terms of operant schedules of reinforcement, their feedback functions, short term effects of the operant-based incentive system, and the validity and generality of the operant-based incentive system.

Design of RCSS: Resource Coordination Systems for Surgical Services using distributed communications.

The plans for Resource Coordination for Surgical Services system (RCSS) incorporate a distributed objectbase with a coordinating server. User-centered information screens are customized for each geographic location in surgical services. User interfaces are designed to mimic paper lists and worksheets used by health care providers. Patient-specific and site-specific data will be entered and maintained by providers at each geographic location, but also rebroadcast and displayed for all providers. Although RCSS is primarily a communications system, it will also support review of surgical utilization and operative scheduling.

Effect of Operator Seat Design on Vibration Exposure

A field study was conducted at a large metropolitan subway system to determine vibration attenuation characteristics of train operator seats through a comparative method. To compare operator seats, vibration measurements were made under conditions for which all variables other than the operator seat were constant. This was achieved by carrying out the vibration measurements on a single subway line, using a single train with constant composition throughout the data collection, with a single train operator and using the same operator schedule. The study was carried out in accordance with the measurement and evaluation techniques outlined in the ISO 2631 standard on whole-body vibration developed by the International Organization for Standardization. The results obtained were analyzed to assess the effectiveness of each seat in reducing the mechanical vibrations transmitted to train operators. Results revealed that seats with complex designs and advanced features transmitted 5% and 19% more overall vibration levels to the train operators than those seats with relatively simple designs, the reasons for which could be explained through simple structural and kinematic analysis.

Effect of Operator Seat Design on Vibration Exposure

A field study was conducted at a large metropolitan subway system to determine vibration attenuation characteristics of train operator seats through a comparative method. To compare operator seats, vibration measurements were made under conditions for which all variables other than the operator seat were constant. This was achieved by carrying out the vibration measurements on a single subway line, using a single train with constant composition throughout the data collection, with a single train operator and using the same operator schedule. The study was carried out in accordance with the measurement and evaluation techniques outlined in the ISO 2631 standard on whole-body vibration developed by the International Organization for Standardization. The results obtained were analyzed to assess the effectiveness of each seat in reducing the mechanical vibrations transmitted to train operators. Results revealed that seats with complex designs and advanced features transmitted 5% and 19% more overall vibration levels to the train operators than those seats with relatively simple designs, the reasons for which could be explained through simple structural and kinematic analysis.

O-3-10 - Is paroxetine in post-stroke depression useful?

N-Methyl-d-aspartate (NMDA) antagonists and γ-aminobutyric acid agonists share a number of common pharmacological properties, including motor and anticonvulsant effects. In the present study, site-selective NMDA antagonists were evaluated for potential anxiolytic efficacy and motor impairment in a modified Geller–Seifter conflict procedure, an animal model widely used to screen drugs for anxiolytic effects. Male Sprague-Dawley rats were trained to respond for food reward under a multiple FI 30 s (food only), FR 10 (food+shock) operant schedule. Consistent with the results of previous studies, the benzodiazepines chlordiazepoxide and diazepam selectively increased punished responding and increased response durations at higher doses. The competitive NMDA antagonist CGP 37,849 increased punished responding at some doses, though not selectively, and also increased response duration in both schedule components. The glycine-site modulators milacemide, ACEA 1011 and ACEA 1021, the NR2B-selective polyamine site antagonist eliprodil and NMDA did not produce anticonflict effects at any dose and had inconsistent effects on response durations. These results suggest that the anticonflict effects of NMDA antagonists are not as reliable as those of the benzodiazepines. Further research is needed to clarify the experimental conditions under which the anxiolytic potential of NMDA antagonists is most evident.

Mechanisms of sickness-induced decreases in food-motivated behavior

Interleukin-1β (IL-1β) is a cytokine released by activated macrophages and monocytes, which mediates many of the local and systemic responses to inflammation. Interleukin-1β induces anorexia in rats when administered peripherally or centrally. An endogenous antagonist for the IL-1 type I receptor has been characterized and cloned (IL-1ra). We have used this protein to ascertain the site of action for the anorexic effects of IL-1β. Male rats were food restricted and trained on an operant schedule for food reinforcement. Administration of recombinant human IL-1β (4 μg IP or 40 ng ICV) induced profound decreases in operant responding, with maximal effects 1–4 h post-injection. Interleukin-1ra pretreatment (2.4 mg IP or 24 μg ICV) completely blocked these effects when administered by the same route. In contrast, ICV IL-1ra only partially blocked the effects of IP IL-1β, and IP IL-1ra was unable to block the effects of ICV IL-1β. Interleukin-1ra did not affect responding by itself. These results suggest that IL-1β acts at both peripheral and central IL-1 receptors to reduce food-motivated behavior. To determine the central site of action of IL-1β, small quantities of IL-1β (5 and 30 ng) were infused into the ventromedial hypothalamus of male rats. Both doses produced profound decreases in responding; the magnitude and time course of these effects were nearly identical to those observed after ICV administration. These results suggest that the VMH may serve as a central site of action for the depressive effects of IL-1β on food intake. There is much controversy over the pathways of communication from the immune system to the brain. To test the hypothesis that the peripheral immune stimulus is transmitted to the brain via a neural communication pathway, mice were injected with lipopolysaccharide at a behaviorally active dose (10 μg IP). This treatment increased the concentrations of substance P, neurokinin A, and calcitonin gene-related peptide in mouse spinal cord in a prostaglandin-dependent manner. Maximal increases in neuropeptide content were observed 1 h post-injection. Finally, subdiaphragmatic vagotomy was found to attenuate the reduction in food-motivated behavior induced by both IL-1β and lipopolysaccharide in mice.