Fixed-ratio Component Research Articles

Behavioral effects of CGS 8216 alone, and in combination with diazepam and pentobarbital in dogs

Beagle dogs (N=3) responded under a multiple fixed-interval (FI) 300 sec, fixed-ratio (FR) 30 schedule of food presentation. The pyrazoloquinoline derivative CGS 8216, given either intravenously (0.01–3.0 mg/kg) or orally (0.1–30.0 mg/kg) had little effect on either the rate or temporal pattern of responding during either component. Both diazepam (0.3 to 17.5 mg/kg, PO) and pentobarbital (0.1–17.5 mg/kg, PO) produced qualitatively similar effects on behavior. Rates of responding during the FI components first increased, then decreased with increasing doses; both drugs produced only dose-related decreases in the rate of responding during the FR components. CGS 8216 antagonized some of the behavioral effects of diazepam; FI and FR response rates returned to baseline, however the effects of diazepam on quarter-life values were not appreciably altered by CGS 8216. The effects of pentobarbital on schedule-controlled responding were not antagonized by CGS 8216. These results indicate CGS 8216 is a selective benzodiazepine antagonist that does not produce benzodiazepine-like behavioral effects.

Effects of chlorpromazine on fixed-ratio responding: modification by fixed-interval discriminative stimuli.

Effects of chlorpromazine (1 to 100 mg/kg) were assessed on two pigeons' responding under various modifications of a multiple schedule of food delivery. During a fixed-interval component, the first response after 5 min produced food; during the subsequent, fixed-ratio component, the 30th response produced food. Modifications of the schedule entailed changes in stimulus conditions imposed during the fixed-ratio component that did not systematically alter characteristics of performance under non-drug conditions. In the first phase of the experiment, distinctive visual stimuli were correlated with each schedule component (conventional multiple schedule); chlorpromazine produced small decreases in fixed-ratio responding (20% at 30 mg/kg). When each response during the fixed-ratio component produced the stimulus correlated with the fixed-interval schedule (fixed-interval discriminative stimulus) for 1.2 s, effects of chlorpromazine were not different from those under the conventional multiple schedule. Chlorpromazine produced greater decreases in fixed-ratio responding (55% at 30 mg/kg) when either the first response of each fixed ratio changed the stimulus correlated with the fixed-ratio schedule to the fixed-interval discriminative stimulus for the remainder of the fixed-ratio component, or when the fixed-interval discriminative stimulus was presented independently of responding according to a matched temporal sequence. When the fixed-interval discriminative stimulus was present continuously during the fixed-ratio component (mixed schedule), chlorpromazine produced even more substantial decreases in fixed-ratio responding (greater than 80% at 30 mg/kg). Effects of chlorpromazine on fixed-interval responding were also modified by the schedules of fixed-interval discriminative stimulus presentation. The effects of chlorpromazine were a joint function of the stimuli prevailing during the multiple schedule and the degree to which responding influenced these stimuli.

Disruption of schedule-controlled behavior by Ro 15-1788 one day after acute treatment with benzodiazepines.

The behavioral effects of the benzodiazepine antagonist Ro 15-1788 were studied in squirrel monkeys after acute injections of benzodiazepines. Monkeys responded under a multiple schedule of food presentation with alternating fixed-interval (FI) and fixed-ratio (FR) components, Chlordiazepoxide (10 mg/kg) increased FI responding and had little effect on FR responding 1 h after it was administered; FI responding was still elevated during the session on the following day. When Ro 15-1788 (0.1-3 mg/kg) was administered 1 h after chlordiazepoxide, it antagonized the effects of chlordiazepoxide in a dose-related manner. When Ro 15-1788 was administered 1 day after chlordiazepoxide, however, doses of 1 or 3 mg/kg suppressed both FI and FR responding. Suppression of schedule-controlled responding was also observed when Ro 15-1788 (3 mg/kg) was administered 1 day after diazepam (3 or 5.6 mg/kg) or N-desmethyldiazepam (5.6 mg/kg). The results show that Ro 15-1788 can precipitate disruption of schedule-controlled behavior 1 day after acute treatment with benzodiazepines.

Effects of MK-212 (6-chloro-2[1-piperazinyl]pyrazine) on schedule-controlled behavior and their reversal by 5-HT antagonists in the pigeon

The effects of MK-212 (6-chloro-2[l-piperazinyl]pyrazine), a centrally-active 5-hydroxytryptamine (5-HT; serotonin) agonist, were studied alone and in combination with the 5-HT antagonists, methysergide (0.01–0.1 mg/kg), metergoline (0.01–1.0 mg/kg) and ketanserin (0.01–3.0 mg/kg). Pigeons were maintained under a procedure where key pecks were reinforced under a multiple fixed-interval (FI) fixed-ratio (FR) schedule of food presentation. In the fixed-interval component, the first response after 3 min had elapsed, produced food, while in the fixed-ratio component, the thirtieth response was reinforced. The drug MK-212 (0.1–3.0 mg/kg) produced dose-related decreases in response rates under both components of the schedule. In smaller doses of MK-212 (0.3 and 1.0 mg/kg), the decrease in the response rate was greater in the fixed-interval component than in the fixed-ratio component. Small doses of methysergide (0.03 mg/kg) and metergoline (0.1 mg/kg), which had little effect when given alone, partially blocked the effects of MK-212 (1.7 and 3.0 mg/kg) in decreasing rate. Larger doses of these compounds, which sometimes increased the response rate when given alone, resulted in a more complete restoration of response rates when administered with MK-212. Ketanserin, a selective 5-HT 2 antagonist, reversed the effects of MK-212 in some cases, but the patterning of responses remained disturbed. These results demonstrate that MK-212 was able to disrupt a complex behavioral task in the pigeon at doses which caused no other noticeable signs, and that these effects were reversed in a systematic way by serotonin antagonists, known to exert a similar antagonism of the effects of MK-212 on other behavioral responses.

ORAL DRUG SELF‐ADMINISTRATION IN RHESUS MONKEYS: INTERACTIONS BETWEEN DRUG AMOUNT AND FIXED‐RATIO SIZE

During daily 3-hr sessions, 5 rhesus monkeys drank drug solutions and water that were concurrently available. The drug solutions were: 1 milligram per milliliter (mg/mL) pentobarbital (2 monkeys), 1 mg/mL pentobarbital plus 0.5% ethanol (1 monkey), 1 mg/mL pentobarbital plus 1% ethanol (1 monkey), and 8% ethanol (1 monkey). The drug solution and water were available under identical two-component tandem fixed-ratio continuous-reinforcement N schedules. Two variables were manipulated: the size of the fixed-ratio component and the number of liquid deliveries (N) in the second component. Deliveries of the drug solution maintained higher rates of responding than did deliveries of the drug vehicle, water. The number of drug deliveries per session increased with increases in the number of deliveries per fixed ratio and decreased with increases in fixed-ratio size. Analysis of the results in terms of the proportion of deliveries to responses showed that the number of drug deliveries per session was directly related to the size of this quotient. Finally, when fixed-ratio size was repeatedly doubled, the following orderly relationship emerged: The greater the number of available drug deliveries per fixed ratio, the less was the percent decrease in the number of fixed ratios completed per session. It was concluded that increases in the number of liquid deliveries per fixed ratio resulted in increases in reinforcing efficacy.

Pyrazoloquinoline benzodiazepine receptor ligands: Effects on schedule-controlled behavior in dogs

The effects of diazepam and the pyrazoloquinoline benzodiazepine receptor ligands CGS8216, CGS9896 and CGS9895 on schedule-controlled responding were studied in dogs. Responding was maintained under a multiple fixed-interval (FI) 5-min fixed-ratio (FR) 30 response schedule of food presentation. Diazepam (PO) produced dose-related decreases in response rates under FR component. Under the FI, rates first increased and then decreased with increasing doses of diazepam. Diazepam also produced a dose-related disruption of the temporal pattern of responding under the FI as measured by decreases in quarter-life values. CGS8216 IV produced dose-related decreases in response rates under both components. The highest oral dose of CGS8216 also decreased rates in both components. CGS8216 was approximately 100 times more potent by the IV route as compared to the oral route. CGS9896 IV had no significant effect on responding under either component of the multiple schedule. However, with increasing doses of CGS9896 PO, response rates under components first decreased and then returned to control values. CGS9895 PO was without significant effect on responding. When CGS8216 was administered concomitantly with graded doses of diazepam, the former drug blocked the rate-decreasing effects of diazepam under the FR component, but not the rate-increasing effects of diazepam under the FI. The present results demonstrate that although these three pyrazoloquinolines are benzodiazepine receptor ligands, they do not exhibit diazepam-like effects on schedule-controlled behavior.

Control of the temporal location of schedule-induced attack in pigeons

Pigeons were exposed to complex fixed-ratio schedules to assess whether the temporal location of schedule-induced attack was controlled by the discriminative properties of food or by the aversive aftereffects of food withdrawal. When exposed to a multiple fixed-ratio 25 fixed-ratio N schedule in which either fixed-ratio component occurred with equal probability according to a quasi-random sequence and in which the value of N ranged from 115 to 150 across subjects, all pigeons exhibited post-food attack against a rear-projected conspecific target predominantly at the signalled onset of the higher-valued ratio component. Exposure of subjects to a mixed fixed-ratio 25 chained fixed-ratio 25 fixed-ratio N-25 schedule, however, resulted in a shift of attack to the signalled onset of the fixed-ratio N-25 component rather than following food. A chained fixed-ratio 25 fixed-ratio N-25 schedule induced attack predominantly after food delivery rather than at the onset of the fixed-ratio N-25 component. These findings show that the temporal locus of schedule-induced attack is primarily controlled by a stimulus, whether food delivery or key color change, that reliably precedes a relatively long period of reinforcer unavailability.

Effects of thyrotropin-releasing hormone (TRH) and MK-771 on behavior of squirrel monkeys controlled by noxious stimuli

The effects of TRH (0.1–30 mg/kg) and an enzyme-resistant analogue, MK-771 (0.1–10 mg/kg), were characterized in squirrel monkeys on responding maintained in the presence of different visual stimuli by a multiple 3-min fixed-interval (FI), 30-response fixed-ratio (FR) schedule of stimulus-shock termination or by a multiple 5-min FI schedule of food or shock presentation. Under the termination schedule, the first response at the end of 3 min in the FI component or the completion of the 30-response requirement in the FR component terminated the visual stimulus in the presence of which shocks occurred (escape schedule). Under the schedule of food or shock presentation, the first response at the end of the 5-min FI produced food in the presence of red stimulus lights or shock in the presence of white lights. TRH and MK-771 produced large, dose-related increases in responding maintained under the FR stimulus-shock termination schedule whereas these peptides produced smaller increases or did not affect responding under the FI schedule. TRH and MK-771 also produced marked increases in responding maintained by shock presentation at doses that did not alter or decreased food-maintained responding in the same subject. Thus, performances maintained by noxious stimuli are uniquely sensitive to the rate-increasing effects of TRH and MK-771. These findings suggest that the behavioral effects of the neuropeptides, TRH and MK-771, can depend on the specific consequences of behavior and, as such, the effects of these substances are determined by many of the same variables that determine the effects of other behaviorally-active drugs.

Effects of barbiturates and other sedative hypnotics in pigeons trained to discriminate phencyclidine from saline.

Pigeons were trained to peck the center key (lighted white) of three response keys to turn off the center keylight and to light one of the side keys with a red keylight and the other side key with a green keylight. Five responses (fixed-ratio component) on either side key relighted the center key. Food was delivered following 10 fixed-ratio components on the red key if 1.5 mg/kg phencyclidine had been given before the session. The position of the red and green keylights on the side keys varied randomly each time they were lighted by a peck on the center key. Subsequently, increasing doses of phencyclidine, barbital, amobarbital, phenobarbital, methaqualone, methyprylon, diazepam, oxazepam, and d-amphetamine were substituted for the training dose of phencyclidine, using a cumulative dosing procedure. At low doses of the sedative hypnotics, birds pecked the keylight color associated with saline. At higher doses, birds pecked both key colors. At the highest doses of pentobarbital and amobarbital, some birds responded almost exclusively On he color associated with phencyclidine. When responding on keys of both colors occurred following administration of phencyclidine or other sedative hypnotics, this responding was controlled by key position rather than by key color.

12-year retention of stimulus and schedule control

After having initially been trained for a classroom demonstration, a pigeon was tested for retention following a 12-year period without intervening training. Strong evidence was obtained of stimulus control and substantial evidence was found of schedule control by the fixed-interval and fixed-ratio components of the multiple schedule used in initial training.

Effects of apomorphine on elicited and operant pecking in pigeons.

The effects of apomorphine (0.001--32.0 mg/kg) on elicited and operant pecking were studied in pigeons. Elicited pecking was measured in a 1-h observation test. Apomorphine caused dose-related increases in the pecking elicited by the drug in all the subjects, with maximal responding at 3.2 mg/kg. In contrast, operant responding on a multiple, 5 min fixed interval, 30 response fixed-ratio schedule revealed individual differences in sensitivity to the drug. A dose of 0.32 mg/kg eliminated key pecking in fixed-interval and fixed-ratio components in 4 (group 1) of the 15 subjects while 3.2 mg/kg eliminated responding in 9 other subjects (group 2), and 2 of the subjects (group 3) required 32.0 mg/kg to eliminate responding. The 13 birds in groups 1 and 2 showed decreases in operant responding with concomitant increases in elicited pecking. For the 2 remaining birds, increases in operant behavior were highly correlated with increased stereotypy. The effects of apomorphine on operant behavior appeared to depend on induced stereotypy, with rate-decreasing effects resulting from the disruption of ongoing behavior by stereotyped pecking aimed elsewhere in the chamber, and rate increases resulting from the redirection of elicited pecking towards the operant key.

MIRROR PECKING AND TIMEOUT UNDER A MULTIPLE FIXED‐RATIO SCHEDULE OF FOOD DELIVERY

Pigeons were trained to peck a key under a multiple fixed-ratio 25 fixed-ratio 175 schedule of food presentation. In the first condition, either a mirror or the opportunity to produce a 30-second timeout were available. In a second condition, mirror and timeout availability were reversed for the two groups. Following a return to the initial condition, mirror and timeout keys were presented together for all birds. Mirror and timeout responses occurred predominantly in the pause in the larger fixed-ratio component, regardless of whether the opportunities for the two responses were available singly or together. Mirror responding occurred in a greater proportion of the pauses than did timeouts. When the opportunities for both mirror pecking and timeout were available concurrently, they occurred with probabilities similar to those under the single conditions. Within the pause itself, mirror responses most frequently occurred immediately after reinforcement. Timeouts occurred most frequently toward the end of the pause, and some timeouts occurred in the early part of the run. Longer preratio pausing occurred in the larger fixed-ratio component in the conditions in which the mirror was present, whether or not any mirror pecks were recorded.

ALTERNATIVE FIXED‐RATIO FIXED‐INTERVAL SCHEDULES OF REINFORCEMENT

Five rats were trained under alternative fixed-ratio fixed-interval schedules, in which food reinforcement was provided for the completion of either a fixed-ratio or a fixed-interval requirement, whichever was met first. Overall response rate and running rate (the rate of responding after the postreinforcement pause) decreased for all subjects as the fixed-ratio value increased. As the proportion of reinforcements obtained from the fixed-ratio component increased and the alternative schedule approached a simple fixed ratio, overall response rate and running rate both increased; conversely, as the proportion of reinforcements obtained from the fixed-interval component increased and the alternative schedule approached a simple fixed interval, response rates decreased. Postreinforcement pause length increased linearly as the average time between reinforcements increased, regardless of the schedule parameters. A break-run pattern of responding was predominant at low- and medium-valued fixed ratios. All subjects displayed at least occasional positively accelerated responding within interreinforcement intervals at higher fixed-ratio values.

Effects of clozapine, chlorpromazine and haloperidol on schedule-controlled behavior

The effects of clozapine, chlorpromazine, and haloperidol were determined in mice and pigeons responding under a multiple fixed-ratio 30, fixed-interval 600 sec schedule of food presentation. In both species, low doses were without effect and moderate to high doses of all three antipsychotics decreased responding. In contrast to other behavioral tests used to predict antipsychotic activity, clozapine was equipotent or more potent than chlorpromazine in decreasing responding under the multiple-fixed-ratio 30, fixed-interval 600 sec schedule. The order of potency observed in the mouse was: haloperidol > chlorpromazine ⩾ clozapine. The order of potency in the pigeon was: haloperidol > clozapine > chlorpromazine. In mice and pigeons, the rate of responding under the fixed-ratio component was decreased at lower than, or the same doses of clozapine as that required to decreased fixed-interval responding. However, in both species, chlorpromazine and haloperidol decreased fixed-interval responding at lower doses or the same dose as that required to decrease fixed-ratio responding.

Effects of quipazine on behavior under a multiple schedule of reinforcement

The effects of three doses of quipazine (1.0, 5.0 and 10.0 mg/kg) on the performance of rats under a multiple fixed-ratio 15 fixed-interval 60-sec schedule of food reinforcement were examined. In the absence of drug, response rates under the fixed-ratio component were much higher than response rates under the fixed-interval component. Rates under the fixed-ratio component were decreased by quipazine in dose-dependent fashion, while response rates under the fixed-interval component were increased by the lowest dose and decreased by the two higher doses of the drug.

CONSERVATION, CHOICE, AND THE CONCURRENT FIXED‐RATIO SCHEDULE

Five rats got all of their water in daily 60-minute sessions. Two levers and a water spout were freely available throughout baseline sessions. Contingency sessions offered a choice between two alternative fixed-ratio components, in the form of a choice between the two levers. Each component required a specified number of lever presses for access to the spout, and then a specified number of licks for another choice between components. Given the observed relative frequency, the absolute frequency of selecting each component was predicted accurately by assuming that the subject conserved between baseline and contingency the total amount of a dimension attributable to lever pressing and licking. Several quantitative models for predicting relative frequency were examined. The best of these assumed that the subject would show a nonexclusive preference for the component requiring fewer lever presses.

Ethanol and isopropanol effects on schedule-controlled responding.

The effects of ethanol and isopropanol were studied on responding by pigeons under multiple fixed-ratio (FR), fixed-interval (FI) schedules of food presentation and under a fixed-interval (FI) schedule of food presentation where responding was decreased by punishment. The ethanol was rapidly absorbed into blood and decreased responding within 15 min after intubation to the opening of the proventriculus. Dose-effect determinations of the effects of ethanol showed that ethanol decreased responding in both the FR and FI components of the multiple schedules at similar doses, but there were increases in responding under an FR 100 schedule at lower doses. Isopropanol tended to decrease FR responding at doses that either increased FI responding or did not affect FI responding. Both ethanol and isopropanol (1 g/kg) produced effects on the local rates of responding within the FI which were rate-dependent in that they increased low rates while not affecting or actually decreasing the high rates of responding. Both ethanol and isopropanol increased punished responding if it was not severely suppressed by the punishment procedures.

Maintenance of observing responses with the less highly valued stimulus in pigeons

Previous research has shown that the more valued stimulus will maintain observing responses but the less valued stimulus will not. In the first part of this experiment, it was shown that the removal of the stimulus associated with the fixed-ratio component of a multiple schedule (mult FI 2 min, FR 35) abolished observing responses. In the next part, the ratio stimulus was phased out by making it available during some ratios but not during others. Observing responses were maintained following the phasing procedure even when all ratio stimuli were unavailable. In the third part, all stimuli, both ratio and interval, were unavailable. Observing responses declined under this condition and increased again when the stimulus associated with the interval was again made available. It is hypothesized that observing responses will be maintained as long as they permit the maintenance of a discrimination.

INDUCED ATTACK DURING MULTIPLE FIXED‐RATIO, VARIABLE‐RATIO SCHEDULES OF REINFORCEMENT1

TWO PIGEONS WERE EXPOSED TO A MULTIPLE SCHEDULE OF REINFORCEMENT: in the presence of one discriminative stimulus, key pecks produced grain according to a fixed-ratio schedule; in the presence of a second discriminative stimulus, key pecks produced grain according to a variable-ratio schedule. The key-peck requirements in the two components were increased in successive stages from 50 to 125 responses. Live target pigeons were restrained at the rear of the chamber. Attacks against the targets were automatically recorded, and a variety of measures of attack behavior were taken. Attacks, when they occurred, always followed grain presentation. All measures revealed higher levels of attack during the fixed-ratio component at all parameter values. All measures generally increased with increases in fixed-ratio values with both birds, and with increases in variable-ratio values with one bird. With the other bird, only the per cent of reinforcements followed by attack increased with increases in variable-ratio value; all other measures first increased and then decreased. Both increasing and bitonic functions relating induced attack to schedule parameters have been reported in experiments usually employing a single measure of attack. The measures have varied widely among these experiments. It is suggested that further studies of induced attack examine a wider range of schedule parameters and that relationships among measures be studied.

Methamphetamine effects on responding under a multiple schedule of shock presentation

Squirrel monkeys responded under a multiple 3-min variable-interval (VI) 10-response fixed-ratio (FR) schedule of response-dependent electric shock presentation. Methamphetamine (0.01-0.17 mg/kg) produced dose-dependent increases in relatively low rates of responding whether these occurred during the FR or the VI component of the schedule. In the one monkey with a relatively high control rate of responding during the VI component, methamphetamine only produced decreases in responding. Responding during the FR component was increased by methamphetamine, even in the monkey whose responding appeared to be suppressed during this component. Previous experiments have shown only further decreases after amphetamines in responding suppressed by response-dependent shock. The present experiments indicate that, in addition to the frequency and intensity of the electric shock and to the schedule maintaining the reference behavior, the nature of the event maintaining the reference behavior can be important in determining the effects of amphetamines. The effects of methamphetamine depend not only on the intensive and temporal characteristics of the ongoing schedule-controlled behavior itself, but also on the past and present context in which the behavior occurs.