Fixed-ratio Component Research Articles

Effects of advance notice on transition-related pausing in pigeons.

Transitions between tasks can produce behavioral disruptions that are characterized as problematic. Advance notice, a procedure designed to reduce disruptions, involves presenting a stimulus to warn of the end of the ongoing activity and the nature of the upcoming activity. Clinical evaluations of advance notice have produced mixed results. We studied advance notice in a controlled laboratory setting. Pigeons' keypecking was maintained on a multiple schedule with 2 fixed-ratio components. In the lean component, completing the ratio produced brief access to food; in the rich component, completing the ratio produced longer access. Disruptions in operant behavior, measured as pauses in pecking, were reliably produced in the transition from a rich component to a lean one. Advance notice was provided by flashing the houselight before transitions to lean components. Advance notice did not reduce pausing in the rich-lean transition; instead, it tended to increase it. When the flashing houselight warned of a transition but was equally likely to be followed by the rich component as the lean one, the stimulus had no reliable effect on pausing. Despite its limitations as a translational model of clinical settings, this experiment suggests that clinical use of advance notice should be approached with caution.

Design and evaluation of a touchscreen apparatus for operant research with pigeons.

We developed a touchscreen apparatus for pigeons and conducted a series of experiments that assessed its utility for free-operant procedures. The apparatus incorporated an on-board Windows computer, an electromechanical interface, an amplified speaker, and the touchscreen. We found that merely projecting a virtual key on the screen was insufficient; too many pecks missed the key. Adding a visual target in the center of the key and providing visual feedback for on-key pecks both failed to improve response accuracy. Accuracy was improved by imposing a timeout after off-key pecks or providing a physical boundary around the key. With the physical boundary, response accuracy was comparable to that obtained with conventional plastic keys, and response acquisition via autoshaping also was comparable. Mixing the color elements of the screen's pixels produced color stimuli, but the colors did not function as pure wavelengths of light in tests of stimulus generalization. Both colors and geometric shapes functioned as discriminative stimuli in multiple schedules with variable-interval and extinction components or rich and lean fixed-ratio components. In general, our touchscreen apparatus is a viable alternative to conventional pigeon chambers and increases the experimenter's options for visual stimuli, auditory stimuli, and the number and location of response keys.

Effect of Intracerebroventricular Injection of TiO<SUB>2</SUB> Nanoparticles on Complex Behaviour in the Rat

There are no data available on the behavioural effects of centrally administered nanoparticles in freely moving intact mammals. Consequently, in the current study male Sprague-Dawley rats were trained to respond under an alternating-lever cyclic-ratio (ALCR) schedule of food reinforcement. Under this schedule, ascending and descending sequences of fixed-ratio (FR) lever press requirements for food reinforcement were presented over six cycles, with each discrete FR component completed on the alternate lever to the previous component. The final version of the schedule was comprised of an ascending followed by a descending sequence of the ratio values 2, 6, 12, 20, 30, 42 and 56, repeated over six cycles. When the rats were able to complete this version of the ALCR schedule in 40 min, each was implanted with a permanently indwelling ICV cannula aimed at the lateral ventricle of the brain, and allowed to recover for 7 days. On the first day of the experiment, all rats were injected with either titanium dioxide (TiO2, 9 nm, stabilised with gallic acid, 10 microl volume, 2 mg/ml) nanoparticles, or 10 microl saline (control). Two-hours after the ICV injections, the behaviour of all rats was measured using the ALCR schedule, and their behaviour was also measured (no ICV injection) for the next 7 days. Under the ALCR schedule, the number of lever-switching errors and incorrect lever perseverations significantly increased in the TiO2 group (p < 0.05). Other parameters of the ALCR schedule (RRRs and PRPs), which indicate the induction of malaise or general motor retardation, were not altered following ICV TiO2 injection. The findings of the current study indicate that central administration of TiO2 nanoparticles induced behavioural deterioration in freely moving intact animals, that the induced behavioural deterioration was a result of central rather than peripheral outcomes, and that this effect was chronic rather than acute.

Abuse pattern of toluene exposure alters mouse behavior in a waiting-for-reward operant task

Abuse Pattern of Toluene Exposure Alters Mouse Behavior in a Waiting-for-Reward Operant Task. Bowen, S.E. and McDonald, P., Neurotoxicology and Teratology, 2008. Inhaling solvents for recreational purposes continues to be a world-wide public health concern. Toluene, a volatile solvent in many abused products, adversely affects the central nervous system. However, the long-term neurobehavioral effects of exposure to high-concentration, binge patterns typical of toluene abuse remain understudied. We studied the behavioral effects of repeated toluene exposure on cognitive function following binge toluene exposure on behavioral impulse control in Swiss Webster mice using a “wait-for-reward” operant task. Mice were trained on a fixed-ratio (FR) schedule using sweetened milk as a reward. Upon achieving FR15, a wait component was added which delivered free rewards in the absence of responses at increasing time intervals (2s, 4s, 6s, etc…). Mice continued to receive free rewards until they pressed a lever that reinstated the FR component (FR Reset). Once proficient in the FR-Wait task, mice were exposed to either 1000 ppm, 3600 ppm or 6000 ppm toluene, or 0ppm (air controls) for 30 min per day for 40days. To avoid acute effects of toluene exposure, behavior was assessed ~22–23 h later. Repeated toluene exposure decreased response rates, the number of FR resets, and increased mean wait time, resulting in a higher response-to-reinforcer ratio than exhibited by controls. Mice receiving the higher exposure level (6000 ppm) showed a dramatic decrease in the number of rewards received, which was reversed when toluene exposure ceased. Mice receiving the lower exposure level (1000 ppm) showed little change in the number of rewards. These results indicate that repeated binge exposures to high concentrations of toluene can significantly interfere with performance as measured by a waiting-for-reward task, suggesting a significant impact on cognitive and/or psychomotor function.

Interactions among unit-price, fixed-ratio value, and dosing regimen in determining effects of repeated cocaine administration

Previous research has shown tolerance to cocaine that was dependent on fixed-ratio (FR) parameter size in the context of a multiple FR schedule of food reinforcement. Completion of the FR requirement in these studies resulted in the same magnitude of reinforcement, regardless of ratio size. The cost-to-benefits ratio (unit-price) was therefore not equated across the different FR components. The current study examined the effects of repeated administration of cocaine to pigeons when unit-price under FR schedules was either the same or different. Additionally, the role of a chronic variable-dosing versus chronic fixed-dosing procedure was examined when unit-price was equated across different ratio values. Pigeons were trained to key peck in daily sessions under a three-component multiple FR schedule of food presentation, according to which either 10, 30, or 100 pecks were required for each delivery of food. In Experiment 1, completion of the FR 10, FR 30, and FR 100 resulted in 1.5, 4.5, and 15.0 s access to food, respectively. That is, the response requirement was correlated with access to food time so that unit-price (pecks per second of access to food) was equated across components. After assessing acute effects of a range of doses of cocaine, drug administration occurred daily before each session, with the dose varying from day to day. Tolerance, the magnitude of which was unrelated to the peck requirement, developed under the repeated-dosing regimen. In order to assess whether having equal unit-price was responsible for producing similar levels of tolerance across components, daily drug administration continued in Experiment 2 using the variable-dose regimen, but the amount of food presented each time was fixed at 4.5 s access to food, yielding different unit-prices under the three pecking requirements. Subsequently, the conditions of Experiment 1 were reinstated, i.e., unit-price was equated. Making unit-price different or the same had little influence on effects of cocaine. In Experiment 3, a fixed dose of cocaine was administered before each session while programmed unit-price remained the same across components. Under these conditions, tolerance became peck-requirement related. Specifically, tolerance was most prevalent under the smaller requirements and less robust or absent when the largest requirement was in effect. Differences in unit-price, therefore, were not related to degree of tolerance, but work requirement was. Differences in effects of cocaine across responses requirements, however, were observed only when each session was preceded by the same dose, not when dose varied from session to session.

Effects of reinforcement magnitude and ratio values on behaviour maintained by a cyclic ratio schedule of reinforcement.

In Experiments 1 and 2, lever pressing by rats was reinforced on a cyclic ratio schedule of food reinforcement, comprising a repeated sequence of fixed-ratio component schedules. Reinforcement magnitude was varied, on occasional sessions in Experiment 1 and across blocks of sessions in Experiment 2, from one to two or three 45-mg food pellets. In the one-pellet condition, post-reinforcement pauses increased with component schedule value. At higher magnitudes, post-reinforcement pauses increased, and overall response rates declined. Response rate on component schedules was a decreasing linear function of the obtained rate of reinforcement in all conditions. Plotted against component schedule value, response rate increased exponentially to an asymptote that decreased when reinforcement magnitude increased. These findings are consistent with regulatory accounts of food-reinforced behaviour. In Experiment 3, rats were trained under a cyclic ratio schedule comprising fixed-ratio components including higher values, and some inverted U-shaped response functions were obtained. Those rats that did not show this relationship were trained on cyclic ratios with even higher values, and all showed inverted U-shaped response functions. This suggests that behaviour on cyclic ratio schedules can reflect activating of reinforcement as well as the satiating effects seen in Experiments 1 and 2.

Effects of reinforcement magnitude and ratio values on behaviour maintained by a cyclic ratio schedule of reinforcement

In Experiments 1 and 2, lever pressing by rats was reinforced on a cyclic ratio schedule of food reinforcement, comprising a repeated sequence of fixed-ratio component schedules. Reinforcement magnitude was varied, on occasional sessions in Experiment 1 and across blocks of sessions in Experiment 2, from one to two or three 45-mg food pellets. In the one-pellet condition, post-reinforcement pauses increased with component schedule value. At higher magnitudes, post-reinforcement pauses increased, and overall response rates declined. Response rate on component schedules was a decreasing linear function of the obtained rate of reinforcement in all conditions. Plotted against component schedule value, response rate increased exponentially to an asymptote that decreased when reinforcement magnitude increased. These findings are consistent with regulatory accounts of food reinforced behaviour. In Experiment 3, rats were trained under a cyclic ratio schedule comprising fixed-ratio components including higher values, and some inverted U-shaped response functions were obtained. Those rats that did not showthis relationship were trained on cyclic ratios with even higher values, and all showed inverted U-shaped response functions. This suggests that behaviour on cyclic ratio schedules can reflect activating of reinforcement as well as the satiating effects seen in Experiments 1 and 2.

Progressive-ratio schedules: effects of later schedule requirements on earlier performances.

Four rats were studied with variants of a progressive-ratio schedule with a step size of 6 in which different terminal components followed completion of the 20th ratio: (a) a reversal of the progression, (b) a fixed-ratio 6 schedule, or (c) extinction. Responding in the progressive-ratio components of these schedules was compared to performances under conventional progressive-ratio baselines. Under baseline conditions, postreinforcement pauses increased exponentially as a function of increasing ratio size, whereas running rates showed modest declines. The procedure of linking the progressive-ratio schedule to the reversed progression or to the fixed-ratio component resulted in decreased pausing. Linking the progressive-ratio schedule to the extinction component had the opposite effect, that of producing weakened progressive-ratio performances as evidenced by increased pausing. Subjects whose responses were reinforced on half of the ratios also showed exponential increases; however, pauses were substantially shorter following ratios on which the reinforcer was omitted. The results suggested that progressive-ratio pausing reflects the influence of remote as well as local contingencies.

Effect of postnatal exposure to a PCB mixture in monkeys on multiple fixed interval-fixed ratio performance.

Behavioral impairment as a consequence of PCB exposure beginning in utero has been reported in both humans and animals. The present study assessed the behavioral consequences of postnatal exposure to PCBs. Male monkeys (Macaca fascicularis) were dosed from birth to 20 weeks of age with 7.5 microgram(s)/kg/day of a PCB mixture representative of the PCBs typically found in human breast milk (eight monkeys) or vehicle (four monkeys). At 4 years of age, performance under a multiple fixed interval (FI)-fixed ratio (FR) schedule of reinforcement was assessed. The FI component was more sensitive to disruption as a result of PCB exposure than was the FR component. PCB-exposed monkeys displayed shorter mean interresponse times (IRTs) than controls, particularly during the earlier sessions of the experiment. Similarly, the increase in pause time characteristic of the acquisition of typical FI performance emerged more slowly across sessions in the PCB-treated group. However, the number of short IRTs (less than 5 s) remained greater in the treated group compared to controls over the 48-session duration of the experiment. On the FR component, control monkeys decreases the mean pause time across sessions whereas the PCB-treated group did not; there were no differences between groups for absolute value of average IRT or pause time. The results of this study extend previous research in this cohort of monkeys, and provide further evidence that PCB exposure limited to the early postnatal period and resulting in environmentally relevant body burdens produces long-term behavioral effects.

Evaluation of transient forebrain ischemia induced by four vessel occlusion using schedule-controlled behavior

Transient (5-min) global forebrain ischemia, induced by four- vessel occlusion, was assessed using a multiple fixed-ratio, fixed-interval schedule of food presentation in five rats. Under control conditions, the schedule produced distinctive response rates in each schedule component. Initially, ischemia disrupted responding under both schedule components, and to approximately the same degree. In general, total session responses returned to pre-occlusion levels during the course of 45 post-occlusion days, however, response rates under the fixed-interval component showed slightly less recovery than those under the fixed-ratio component. Histological assessment revealed considerable variability in hippocampal damage between rats. Severe damage in the CA1, CA2, and CA3 formations was observed in a single rat, and that rat also showed the greatest degree of response disruption. These results suggest that schedule-controlled responding may be a valuable method for assessing the effects of ischemic injury, and thus, putative neuroprotective compounds, on complex behavior.

Effects of cocaine and ethylcocaine on schedule-controlled responding in rats

The effects of cocaine and benzoylecognine ethyl ester (ethylcocaine), its metabolite found only in simultaneous users of cocaine and ethanol, were studied in rats responding for food under a multiple fixed-ratio fixed-interval schedule of food presentation. Both cocaine and ethylcocaine increased rates of responding under the fixed-interval component and decreased the quarter life. Both drugs only decreased rates of responding under the fixed-ratio component. Cocaine was approximately equipotent to ethylcocaine. Ethylcocaine may contribute to interactions between cocaine and ethanol by exerting cocaine-like effects not seen with other cocaine metabolites.

Interaction of sigma and PCP-like drugs on operant behaviors in the rat.

Many PCP-like drugs interact with at least two types of binding sites in the CNS, one of which is linked to excitatory amino acid transmission and the other with an unknown function. The present experiments were designed to further clarify the mechanism of action of drugs in this class. Assessment was made of the effects of PCP, MK-801, (+)-pentazocine, (+)- and (-)-N-allyl-normetazocine (NANM), (+)-amphetamine and BMY-14802 in rats responding under a multiple timeout 600 s (TO), differential reinforcement of low rates 10 s (DRL), fixed ratio (FR) 10 schedule of reinforcement. The effects of the PCP-receptor selective drug MK-801 were compared to those of the mixed sigma/PCP drug (+)-NANM after each were combined with doses of (+)-pentazocine, PCP, BMY-14802, and (+)-amphetamine. MK-801 was also tested in combination with (+)-NANM, as was PCP with BMY-14802. When administered alone, MK-801, PCP, (+)-NANM, (+)-pentazocine, and (+)-amphetamine increased rates of responding under the DRL component of the multiple schedule. The drugs tested generally produced decreases in rates of responding under the FR component. (+)-Pentazocine and BMY-14802 did not modify the effects of (+)-NANM or of MK-801. PCP enhanced the effects of MK-801 and (+)-NANM, and (+)-amphetamine enhanced the effects of MK-801 but not of (+)-NANM. BMY-14802 attenuated the effects of PCP. Taken together, these data suggest similarities as well as some differences in the pharmacologic activities of MK-801 and (+)-NANM and PCP.

EFFECTS OF SCHEDULE OF REINFORCEMENT ON A PENTOBARBITAL DISCRIMINATION IN RATS

The purpose of this study was to determine the effects of the schedule of reinforcement on a pentobarbital discrimination in rats. Five rats were trained to discriminate 10 mg/kg pentobarbital from saline under a multiple fixed-interval 180-s fixed-ratio 20 schedule of reinforcement. During both saline and pentobarbital training sessions, subjects emitted a higher percentage of correct responses under the fixed-ratio component as compared to the fixed-interval component of the multiple schedule. Determination of the pentobarbital dose-response curve under the fixed-ratio component resulted in a steep curve characterized by responding on the saline lever at low doses and on the drug lever at higher doses. Under the fixed-interval component, a graded dose-effect curve was produced, with considerable responding on both levers after intermediate doses of pentobarbital. The administration of phencyclidine and MK-801 resulted in an intermediate level of drug-lever responding for some subjects. Administration of d-amphetamine resulted in saline (nondrug) appropriate responding. The results of this study demonstrate that the schedule of reinforcement is a determinant of drug stimulus control, just as it is a determinant of other drug effects.

The role of response-reinforcer correlation in signaled reinforcement effects

In three experiments, we examined the effects of signaling reinforcement during operant responding in order to illuminate the factors underlying instrumental overshadowing and potentiation effects. Specifically, we examined whether signaling reinforcement produces an enhancement and attentuation of responding when the response-reinforcer correlation is weak and strong, respectively. In Experiment 1, rats responded on variable-ratio (VR) or variable-interval (VI) schedules that were equated for the number of responses emitted per reinforcer. A signal correlated with reinforcement enhanced response rates on the VR schedule, but attenuated response rates were produced by the signal on the VI schedule. In Experiment 2, two groups of rats responded on a VI schedule while the two other groups received a conjoint VI, negative fixed-ratio schedule in which the subjects lost the availability of reinforcements if they emitted high response rates. A reinforcement signal attenuated responding for the simple VI groups but not for the animals given the negative fixed-ratio component, although the signal improved response efficiency in both groups. In Experiment 3, a poor correlation between responding and reinforcement was produced by a VI schedule onto which the delivery of response-independent food was superimposed. A signal for reinforcement initially elevated responding on this schedule, relative to an unsignaled condition; however, this pattern was reversed with further training. In sum, the present experiments provide little support for the view that signaling reinforcement enhances responding when the response-reinforcer correlation is weak and attenuates responding when this correlation is strong.

Fixed-ratio size as a determinant of the development of tolerance to morphine.

The acute and chronic effects of morphine were examined in pigeons exposed to a multiple schedule with fixed-ratio 5, 25, and 125 components. Acute exposure to morphine (0.56-10.0 mg/kg) resulted in rate reductions under each component when the dose was 1 mg/kg or higher. With chronic exposure to 5.6 mg/kg, tolerance to the rate-reducing effects of morphine was evident under each fixed-ratio component. The development of tolerance was determined to some extent by fixed-ratio size, a result similar to earlier findings with cocaine.

Instrumental responding by rats on free-operant schedules with components that schedule response-dependent reinforcer omission: Implications for optimization theories

In two experiments, we assessed whether rats optimize the number of reinforcers per response. In Experiment 1, one group of rats was trained to leverpress for food reinforcement on a simple variable-interval (VI) 60-sec schedule. For another group, a negative fixed-ratio component was imposed on the VI schedule to produce a conjoint contingency in which reinforcement became available on the VI schedule but was omitted when the ratio criterion was satisfied. In Experiment 2, one group of rats responded on a VI schedule and also received response-independent food. For another group, responding above a certain rate canceled the response-independent food. Despite the negative contingency experienced by the groups in Experiments 1 and 2, responding was maintained at a level at which the number of obtained reinforcers was reduced substantially below the maximum number possible. In addition, in both experiments, the groups that experienced the negative contingency responded at a lower rate than did a yoked control group that experienced the same frequency of reinforcement but lacked the negative component. These results demonstrate that although rats do not optimize their behavior with respect to reinforcement, they are nevertheless sensitive to some aspect of the instrumental contingency in operation.

Effects of Ro 15-4513 on schedule-controlled responding of pigeons

The partial inverse benzodiazepine agonist Ro 15-4513 has been found to antagonize some of the behavioral and physiological effects of ethanol, but relatively little is known about the behavioral effects of the drug alone. In the present study, pigeons responding under a multiple fixed-ratio 25 interresponse-time-greater-than-6-sec schedule of food delivery were exposed acutely and chronically to Ro 15-4513. Acute administrations of the drug (1.0, 1.8, 3.2, and 5.4 mg/kg) reduced response rates under the fixed-ratio component at some doses, although two birds were more sensitive to the drug than the third subject. Response rates under the interresponse-time-greater-than-6-sec component were not affected by acute administrations of Ro 15-4513. When 5.4 mg/kg Ro 15-4513 was administered prior to 15 consecutive sessions, tolerance developed to the rate-reducing effects of the drug under the fixed-ratio component. These findings, in contrast to those of early investigations in which gross measures of behavior were employed, suggest that Ro 15-4513 is behaviorally active at relatively low doses.

Interactive Effects of Fixed-Ratio Size and Number of Food Pellets Per Fixed Ratio on Rats’ Food-Reinforced Behavior

In three experiments, albino rats’ lever pressing was reinforced with food pellets under fixed-ratio reinforcement schedules during daily 3-hr sessions. In Experiment 1, fixed-ratio size was varied while one pellet was delivered at the completion of each ratio. Overall response rate was an inverted U-shaped function of fixed-ratio size. As fixed-ratio size was increased, the number of pellets obtained per session remained fairly constant at low and moderate response requirements, then decreased at higher requirements. In Experiment 2, the number of food pellets available under a continuous reinforcement schedule following completion of each fixed-ratio component was varied, while fixed-ratio size was held constant at the highest value reached by each rat during Experiment 1. With increases in the number of pellets available (i.e., In reinforcer magnitude) per fixed ratio, mean numbers of pellets delivered per session increased while mean overall response rate decreased. In Experiment 3, reinforcer magnitudes ranging up to 512 pellets per fixed ratio were delivered at fixed-ratio sizes ranging from 128 to 2048 responses. At each fixed-ratio size, mean overall response rates were inverted U-shaped functions of reinforcer magnitude, while mean number of pellets delivered was related directly to reinforcer magnitude. As fixed-ratio size was increased, progressively larger reinforcer magnitudes maintained the maximum overall response rate. Running rates were uniform across a wide range of reinforcer magnitudes and fixed-ratio sizes. Finally, across each doubling of fixed-ratio size, the relative persistence of behavior increased directly with the magnitude of the reinforcer. The results of Experiment 3 demonstrated that reinforcing effects increased with increasing reinforcer magnitude. Differences in the response-rate results of the three experiments suggest that in many cases reinforcing effects may be more accurately assessed by nonresponse-rate measures.

Behavioral effects of phencyclidine and ketamine alone and in combination with other drugs

The behavioral effects of phencyclidine (PCP) and ketamine administered alone and in combination with naloxone, atropine, methyl atropine, chlorpromazine and d-amphetamine were studied in squirrel monkeys trained to press a response lever under a fixed-ratio 30 schedule maintained by the termination of a stimulus associated with electric shock presentation. Under non-drug conditions, a period of high-rate responding in the presence of the stimulus associated with shock presentation was followed by a period of no responding during a 40-s timeout scheduled between fixed-ratio components. Mean rates of responding fixed-ratio components decreased monotonically as PCP dose increased from 0.1 to 0.56 mg/kg, and doses of 3.0 and 5.6 mg/kg ketamine produced decreases in mean response rate comparable to doses of 0.3 and 0.56 mg/kg PCP. The dose-effect functions revealed that ketamine was approximately one-tenth as potent as PCP. The present data also characterized the time-course effects of PCP and ketamine, with the former having effects that were slower in onset yet more persistent in time. None of the drugs studied in combination with PCP and ketamine provided evidence of a pharmacological antagonism of the behavioral effects of the latter two drugs. Rather, the data indicated an enhancement of behavioral effects when certain drug combinations ere studied.

Effects of fixed-interval duration on the development of tolerance to decreased responding by l-nantradol.

Key pecking of pigeons was maintained under a chained schedule in which the first response after 2 h (fixed interval) was followed by the opportunity to obtain food after sequences of 30 responses (fixed ratio), and animals received acute injections of l-nantradol (0.001-0.1 mg/kg). Smallest doses were ineffective; largest doses decreased all responding; and intermediate doses decreased fixed-interval, but not fixed-ratio, responding. When animals subsequently received daily administration of 0.1 mg/kg l-nantradol prior to experimental sessions, initially decreased fixed-interval responding did not recover during 21 sessions of l-nantradol administration, whereas fixed-ratio responding was demonstrated on several occasions by automatic advancement to the fixed-ratio component. When the schedule was changed so that the same total amount of food was available after ten shorter fixed intervals, fixed-interval responding resumed within a single session, and when the schedule was changed back so that all food was available only after 2 h had elapsed, fixed-interval responding diminished within a few sessions and virtually no responding occurred for 21 additional sessions. The behavioral effects of chronic l-nantradol depended on both the schedule and the parameter of reinforcement.