Quantitative analysis of performance on a progressive-ratio schedule: effects of reinforcer type, food deprivation and acute treatment with Δ9-tetrahydrocannabinol (THC).

Rats' performance on a progressive-ratio schedule maintained by sucrose (0.6M, 50 µl) and corn oil (100%, 25 µl) reinforcers was assessed using a model derived from Killeen's (1994) theory of schedule-controlled behaviour, 'Mathematical Principles of Reinforcement'. When the rats were maintained at 80% of their free-feeding body weights, the parameter expressing incentive value, a, was greater for the corn oil than for the sucrose reinforcer; the response-time parameter, δ, did not differ between the reinforcer types, but a parameter derived from the linear waiting principle (T0), indicated that the minimum post-reinforcement pause was longer for corn oil than for sucrose. When the rats were maintained under free-feeding conditions, a was reduced, indicating a reduction of incentive value, but δ was unaltered. Under the food-deprived condition, the CB1 cannabinoid receptor agonist Δ(9)-tetrahydrocannabinol (THC: 0.3, 1 and 3 mg kg(-1)) increased the value of a for sucrose but not for corn oil, suggesting a selective enhancement of the incentive value of sucrose; none of the other parameters was affected by THC. The results provide new information about the sensitivity of the model's parameters to deprivation and reinforcer quality, and suggest that THC selectively enhances the incentive value of sucrose.

Evidence for a role of 5-HT2C receptors in the motor aspects of performance, but not the efficacy of food reinforcers, in a progressive ratio schedule.

RATIONALE: 5-Hydroxytryptamine2C (5-HT2C) receptor agonists reduce the breakpoint in progressive ratio schedules of reinforcement, an effect that has been attributed to a decrease of the efficacy of positive reinforcers. However, a reduction of the breakpoint may also reflect motor impairment. Mathematical models can help to differentiate between these processes. OBJECTIVE: The effects of the 5-HT2C receptor agonist Ro-600175 ((αS)-6-chloro-5-fluoro-α-methyl-1H-indole-1-ethanamine) and the non-selective 5-HT receptor agonist 1-(m-chlorophenyl)piperazine (mCPP) on rats' performance on a progressive ratio schedule maintained by food pellet reinforcers were assessed using a model derived from Killeen's Behav Brain Sci 17:105-172, 1994 general theory of schedule-controlled behaviour, 'mathematical principles of reinforcement'. METHOD: Rats were trained under the progressive ratio schedule, and running and overall response rates in successive ratios were analysed using the model. The effects of the agonists on estimates of the model's parameters, and the sensitivity of these effects to selective antagonists, were examined. RESULTS: Ro-600175 and mCPP reduced the breakpoint. Neither agonist significantly affected a (the parameter expressing incentive value), but both agonists increased δ (the parameter expressing minimum response time). The effects of both agonists could be attenuated by the selective 5-HT2C receptor antagonist SB-242084 (6-chloro-5-methyl-N-{6-[(2-methylpyridin-3-yl)oxy]pyridin-3-yl}indoline-1-carboxamide). The effect of mCPP was not altered by isamoltane, a selective 5-HT1B receptor antagonist, or MDL-100907 ((±)2,3-dimethoxyphenyl-1-(2-(4-piperidine)methanol)), a selective 5-HT2A receptor antagonist. CONCLUSIONS: The results are consistent with the hypothesis that the effect of the 5-HT2C receptor agonists on progressive ratio schedule performance is mediated by an impairment of motor capacity rather than by a reduction of the incentive value of the food reinforcer.

Effects of SKF-83566 and haloperidol on performance on progressive ratio schedules maintained by sucrose and corn oil reinforcement: quantitative analysis using a new model derived from the Mathematical Principles of Reinforcement (MPR).

RATIONALE: Mathematical models can assist the interpretation of the effects of interventions on schedule-controlled behaviour and help to differentiate between processes that may be confounded in traditional performance measures such as response rate and the breakpoint in progressive ratio (PR) schedules. OBJECTIVE: The effects of a D1-like dopamine receptor antagonist, 8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hydrobromide (SKF-83566), and a D2-like receptor antagonist, haloperidol, on rats' performance on PR schedules maintained by sucrose and corn oil reinforcers were assessed using a new model derived from Killeen's (Behav Brain Sci 17:105-172, 1994) Mathematical Principles of Reinforcement. METHOD: Separate groups of rats were trained under a PR schedule using sucrose or corn oil reinforcers. SKF-83566 (0.015 and 0.03 mg kg(-1)) and haloperidol (0.05 and 0.1 mg kg(-1)) were administered intraperitoneally (five administrations of each treatment). Running and overall response rates in successive ratios were analysed using the new model, and estimates of the model's parameters were compared between treatments. RESULTS: Haloperidol reduced a (the parameter expressing incentive value) in the case of both reinforcers, but did not affect the parameters related to response time and post-reinforcement pausing. SKF-83566 reduced a and k (the parameter expressing sensitivity of post-reinforcement pausing to the prior inter-reinforcement interval) in the case of sucrose, but did not affect any of the parameters in the case of corn oil. CONCLUSIONS: The results are consistent with the hypothesis that blockade of both D1-like and D2-like receptors reduces the incentive value of sucrose, whereas the incentive value of corn oil is more sensitive to blockade of D2-like than D1-like receptors.

Pharmacological studies of performance on the free-operant psychophysical procedure.

In the free-operant psychophysical procedure (FOPP), reinforcement is provided intermittently for responding on lever A in the first half and lever B in the second half of a trial. Temporal differentiation is measured from the psychometric function (percent responding on B, %B, versus time from trial onset, t), the index of timing being T50, the value of t at %B=50. T50 is reduced by acute treatment with 5-hydroxytryptamine (5-HT1A, 5-HT2A) and dopamine (D1-like, D2-like) receptor agonists. The effects of the agonists can be reversed by the respective antagonists of these receptors. Evidence is reviewed suggesting that the effect of endogenous 5-HT is mediated by 5-HT2A receptors and the effect of endogenous dopamine by D1-like receptors. Data are presented on the effects of lesions of the prefrontal cortex and corpus striatum on the sensitivity of performance on the FOPP to D1-like and D2-like receptor agonists. Lesions of the nucleus accumbens, but not the dorsal striatum or prefrontal cortex, attenuated the effects of a D1-like receptor agonist, 6-chloro-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzazepine [SKF-81297], but not a D2-like receptor agonist, quinpirole, on T50. The results indicate that a population of D1-like receptors in the ventral striatum may contribute to the control of timing performance on the FOPP.

Fos expression in the prefrontal cortex and ventral striatum after exposure to a free-operant timing schedule.

It has been proposed that cortico-striato-thalamo-cortical circuits that incorporate the prefrontal cortex and corpus striatum regulate interval timing behaviour. In the present experiment regional Fos expression was compared between rats trained under an immediate timing schedule, the free-operant psychophysical procedure (FOPP), which entails temporally regulated switching between two operanda, and a yoked variable-interval (VI) schedule matched to the timing task for food deprivation level, reinforcement rate and overall response rate. The density of Fos-positive neurones (counts mm(-2)) in the orbital prefrontal cortex (OPFC) and the shell of the nucleus accumbens (AcbS) was greater in rats exposed to the FOPP than in rats exposed to the VI schedule, suggesting a greater activation of these areas during the performance of the former task. The enhancement of Fos expression in the OPFC is consistent with previous findings with both immediate and retrospective timing schedules. Enhanced Fos expression in the AcbS was previously found in retrospective timing schedules based on conditional discrimination tasks, but not in a single-operandum immediate timing schedule, the fixed-interval peak procedure. It is suggested that the ventral striatum may be engaged during performance on timing schedules that entail operant choice, irrespective of whether they belong to the immediate or retrospective categories.

Fos expression in the orbital prefrontal cortex after exposure to the fixed-interval peak procedure.

It has been proposed that cortico-striato-thalamo-cortical circuits that incorporate the prefrontal cortex and dorsal striatum regulate interval timing behaviour. The present experiment examined whether performance on the fixed-interval peak procedure (FIPP), an immediate timing schedule, would induce neuronal activity in cortical and striatal areas, as revealed by enhanced expression of the Fos protein, a marker for neuronal activation. Regional Fos expression was compared between rats trained on the FIPP and rats trained on a variable-interval (VI) schedule matched to the FIPP for overall response rate and reinforcer delivery. Response rate in the peak trials of the FIPP conformed to a temporally differentiated pattern, which was well described by a modified Gaussian function; in agreement with previous findings, the peak time occurred close to the time at which the reinforcer was delivered in the fixed-interval trials, and the Weber fraction was within the range of values reported previously. The density of Fos-positive neurones (counts mm(-2)) in the orbital prefrontal cortex (OPFC) was greater in rats exposed to the FIPP than in rats exposed to the VI schedule, suggesting a greater activation of this area during the performance of the former task. This is consistent with the results of previous studies that have implicated the OPFC in interval timing behaviour. However, there was no significant difference between the levels of Fos expression in the dorsal or ventral striatum of the rats trained under the two schedules.

Effects of amisulpride and aripiprazole on progressive-ratio schedule performance: comparison with clozapine and haloperidol.

Clozapine and some other atypical antipsychotics (e.g. quetiapine, olanzapine) have been found to exert a characteristic profile of action on operant behaviour maintained by progressive-ratio schedules, as revealed by Killeen's Mathematical Principles of Reinforcement model of schedule-controlled behaviour. These drugs increase the value of a parameter that expresses the 'incentive value' of the reinforcer (a) and a parameter that is inversely related to the organism's 'motor capacity' (δ). This experiment examined the effects of two further atypical antipsychotics, aripiprazole and amisulpride, on progressive-ratio schedule performance in rats; the effects of clozapine and a conventional antipsychotic, haloperidol, were also examined. In agreement with previous findings, clozapine (4, 8 mg kg⁻¹) increased a and δ, whereas haloperidol (0.05, 0.1 mg kg⁻¹) reduced a and increased δ. Aripiprazole (3,30 mg kg⁻¹) increased δ but did not affect a. Amisulpride (5, 50 mg kg⁻¹) had a delayed and protracted effect: δ was increased 3-6 hours after treatment; a was increased 1.5 hours, and reduced 12-24 hours after treatment. Interpretation based on Killeen's model suggests that aripiprazole does not share clozapine's ability to enhance reinforcer value. Amisulpride produced a short-lived enhancement, followed by a long-lasting reduction, of reinforcer value. Both drugs impaired motor performance.

Nucleus accumbens and delay discounting in rats: evidence from a new quantitative protocol for analysing inter-temporal choice.

RATIONALE: There is evidence that the core of the nucleus accumbens (AcbC) is involved in inter-temporal choice behaviour. OBJECTIVE: A new behavioural protocol was used to examine the effect of destruction of the AcbC on delay discounting in inter-temporal choice schedules in rats. METHOD: Rats with excitotoxic lesions of the AcbC or sham lesions made repeated choices on an adjusting-delay schedule between a smaller reinforcer (A) that was delivered immediately and a larger reinforcer (B) that was delivered after a delay which increased or decreased depending on the subject's choices. In two phases of the experiment, reinforcer sizes were selected which enabled theoretical parameters expressing delay discounting and sensitivity to reinforcer size to be estimated from the ratio of the indifference delays (i.e. the quasi-stable values of the adjusting delay seen after extended training) obtained in the two phases. RESULTS: In both groups, indifference delays were shorter when the sizes of A and B were 14 and 25 µl than when they were 25 and 100 µl of a 0.6 M sucrose solution. Indifference delays were shorter in AcbC-lesioned than in sham-lesioned rats. Estimates of delay discounting rate based on the ratio of the indifference delays were lower in the AcbC-lesioned than in the sham-lesioned rats. The size sensitivity parameter did not differ between the groups. Adjusting delays in successive blocks of trials were analysed using Fourier transform. The period corresponding to the dominant frequency of the power spectrum and power within the dominant frequency band did not differ between the groups. CONCLUSIONS: Destruction of the AcbC increased the rate of delay discounting.

Effect of orexin-B-saporin-induced lesions of the lateral hypothalamus on performance on a progressive ratio schedule.

It has been suggested that a sub-population of orexinergic neurones whose somata lie in the lateral hypothalamic area (LHA) play an important role in regulating the reinforcing value of both food and drugs. This experiment examined the effect of disruption of orexinergic mechanisms in the LHA on performance on the progressive ratio schedule of reinforcement, in which the response requirement increases progressively for successive reinforcers. The data were analysed using a mathematical model which yields a quantitative index of reinforcer value and dissociates effects of interventions on motor and motivational processes. Rats were trained under a progressive ratio schedule using food-pellet reinforcement. They received bilateral injections of conjugated orexin-B-saporin (OxSap) into the LHA or sham lesions. Training continued for a further 40 sessions after surgery. Equations were fitted to the response rate data from each rat, and the parameters of the model were derived for successive blocks of 10 sessions. The OxSap lesion reduced the number of orexin-containing neurones in the LHA by approximately 50% compared with the sham-lesioned group. The parameter expressing the incentive value of the reinforcer was not significantly altered by the lesion. However, the parameter related to the maximum response rate was significantly affected, suggesting that motor capacity was diminished in the OxSap-lesioned group. The results indicate that OxSap lesions of the LHA disrupted food-reinforced responding on the progressive ratio schedule. It is suggested that this disruption was brought about by a change in non-motivational (motor) processes.

A clozapine-like effect of cyproheptadine on progressive ratio schedule performance.

The atypical antipsychotic drug clozapine has multiple pharmacological actions, some of which, including 5-hydroxytryptamine (5-HT2) and histamine (H1) receptor antagonist effects, are shared by the non-selective 5-HT receptor antagonist cyproheptadine. Atypical antipsychotics have a characteristic profile of action on operant behaviour maintained by progressive ratio schedules, as revealed by Killeen's (1994) mathematical model of schedule controlled behaviour. These drugs increase the values of a parameter that expresses the 'incentive value' of the reinforcer (a) and a parameter that is inversely related to the 'motor capacity' of the organism (δ). This experiment examined the effects of acute treatment with cyproheptadine and clozapine on performance on a progressive ratio schedule of food reinforcement in rats; the effects of a conventional antipsychotic, haloperidol, and two drugs with food intake-enhancing effects, chlordiazepoxide and Δ9-tetrahydrocannabinol (THC), were also examined. Cyproheptadine (1, 5 mg kg⁻¹) and clozapine (3.75, 7.5 mg kg⁻¹) increased a and δ. Haloperidol (0.05, 0.1 mg kg⁻¹) reduced a and increased δ. Chlordiazepoxide (3, 10 mg kg⁻¹) increased a but reduced δ. THC (1, 3 mg kg⁻¹) had no effect. Interpretation based on Killeen's (1994) model suggests that cyproheptadine and clozapine enhanced the incentive value of the reinforcer and impaired motor performance. Motor impairment may be due to sedation (possibly reflecting H1 receptor blockade). Enhancement of incentive value may reflect simultaneous blockade of H1 and 5-HT2 receptors, which has been proposed as the mechanism underlying the food intake-enhancing effect of cyproheptadine. In agreement with previous findings, haloperidol impaired motor performance and reduced the incentive value of the reinforcer. Chlordiazepoxide's effect on a is consistent with its food intake-enhancing effect.

Transitional and steady-state choice behavior under an adjusting-delay schedule.

Twelve rats made repeated choices on an adjusting-delay schedule between a smaller reinforcer (A) that was delivered immediately after a response and a larger reinforcer (B) that was delivered after a delay which increased or decreased by 20% depending on the subject's choices in successive blocks of trials. In two phases of the experiment (100 sessions and 40 sessions), reinforcer sizes were selected which enabled theoretical parameters expressing the rate of delay discounting and sensitivity to reinforcer size to be estimated from the ratio of the indifference delays obtained in the two phases. Indifference delays, calculated from adjusting delays in the last 10 sessions of each phase, were shorter when the sizes of A and B were 14 and 25 µl of a 0.6 M sucrose solution than when they were 25 and 100 µl of the same solution. The ratio of the indifference delays was significantly smaller than that predicted on the basis of an assumed linear relation between reinforcer size and instantaneous reinforcer value, consistent with a previous proposal that this relation may be hyperbolic in form. Estimates of the rate of delay discounting based on the ratio of the two indifference delays (mean, 0.08 s(-1)) were similar to values obtained previously using different intertemporal choice protocols. Estimates of the size-sensitivity parameter (mean 113 µl) were similar to estimates recently derived from performance on progressive-ratio schedules. In both phases of the experiment, adjusting delays in successive blocks of trials were analyzed using the Fourier transform. The power spectrum obtained from individual rats had a dominant frequency that corresponded to a period of oscillation of the adjusting delay between 30 and 100 trial blocks (mean, 78). Power in the dominant frequency band was highest in the early sessions of the first phase and declined with extended training. It is suggested that this experimental protocol may have utility in neurobehavioral studies of intertemporal choice.

Fos expression in the prefrontal cortex and nucleus accumbens following exposure to retrospective timing tasks.

The dorsal striatum and prefrontal cortex have been implicated in interval timing. We examined whether performance of temporal discrimination tasks is associated with increased neuronal activation in these areas, as revealed by Fos expression, a marker for neuronal activation. In Experiment 1, rats were trained on a discrete-trials temporal discrimination task in which a light (22 cd/m²) was presented for a variable time, t (2.5-47.5 s), after which levers A and B were presented. A response on lever A was reinforced if t < 25 s, and a response on lever B was reinforced if t > 25 s. A second group was trained on a light-intensity discrimination procedure, in which a light of variable intensity, i (3.6-128.5 cd/m²) was presented for 25 s. A response on lever A was reinforced if i < 22 cd/m², and a response on lever B was reinforced if i > 22 cd/m². In Experiment 2, bisection procedures were used to assess temporal (200-800 ms, 22 cd/m²) and light-intensity (3.6-128.5 cd/m², 400 ms) discrimination. The increase in proportional choice of lever B as a function of stimulus duration or intensity conformed to a two-parameter logistic equation. Fos expression in the prefrontal cortex and nucleus accumbens was higher in rats performing temporal discrimination tasks than in those performing light-intensity discrimination tasks, indicating greater neuronal activation in these areas during temporal discrimination tasks. Fos expression in the dorsal striatum did not differ between rats performing temporal and light-intensity discrimination tasks. These results suggest that the prefrontal cortex and nucleus accumbens are involved in temporal discrimination.

Choice between reinforcer delays versus choice between reinforcer magnitudes: differential Fos expression in the orbital prefrontal cortex and nucleus accumbens core.

Lesions of the orbital prefrontal cortex (OPFC) and the nucleus accumbens core (AcbC) can disrupt performance in inter-temporal choice tasks, possibly by increasing the organism's sensitivity to delay and/or magnitude of reinforcement. This experiment examined whether exposure to an inter-temporal choice would induce neuronal activation in these areas, as indicated by enhanced expression of the Fos protein. Twelve rats were trained to press levers A and B under an adjusting-delay schedule in which a response on A delivered 50 microl of a sucrose reinforcer after 2 or 18s, whereas a response on B delivered the same reinforcer after a delay that was adjusted in accordance with the rat's choices. Another 12 rats were trained under a similar schedule in which a response on A delivered an immediate reinforcer of size 20 or 180 microl, whereas a response on B delivered an immediate reinforcer whose size was adjusted in accordance with the rat's choices. A third group received training under a schedule that did not entail variation of reinforcer size or delay, or choice between reinforcers, and a control group underwent food restriction without behavioural training. Exposure to the adjusting-delay schedule was associated with enhanced Fos expression in both the OPFC and AcbC, whereas exposure to the adjusting-magnitude schedule was associated with enhanced Fos expression in the OPFC but not the AcbC, compared to the control group. The results are consistent with previous findings that implicated the AcbC and OPFC in delay discounting, and the OPFC in sensitivity to reinforcer size.

Comparison of the effects of 2,5-dimethoxy-4-iodoamphetamine and D-amphetamine on the ability of rats to discriminate the durations and intensities of light stimuli.

Rats' ability to discriminate durations is disrupted by the monoamine-releasing agent D-amphetamine and the 5-HT2 receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). It is unknown whether this effect is specific for temporal discrimination or reflects general disruption of stimulus control. This experiment addressed this question by comparing the effects of D-amphetamine and DOI on temporal discrimination and discrimination along a nontemporal dimension, light intensity. Twelve rats responded on a schedule in which a light (intensity 22 cd/m) was presented for t seconds (2.5-47.5 s), after which levers A and B were presented. Responses on A were reinforced when t was less than 25 s, and responses on B were reinforced when t was greater than 25 s. Twelve rats responded on a similar schedule in which a light of intensity i (3.6-128.5 cd/m) was presented for 25 s. Responses on A were reinforced when i was less than 22 cd/m, and responses on B were reinforced when i was greater than 22 cd/m. Logistic functions were fitted and psychophysical parameters estimated [T50, I50 (central tendency of temporal or light-intensity discrimination); Weber fraction (relative discriminative precision)]. D-Amphetamine (0.2-0.8 mg/kg) increased the Weber fraction for temporal and light-intensity discrimination; DOI (0.625-0.25 mg/kg) increased it for temporal discrimination only. Both drugs increased T50; neither altered I50. D-Amphetamine and DOI have similar effects on temporal discrimination but different effects on light-intensity discrimination. The increase in T50 may reflect the impairment of sustained attention during prolonged stimulus presentation.

Quantitative analysis of the effect of lesions of the subthalamic nucleus on intertemporal choice: further evidence for enhancement of the incentive value of food reinforcers.

Recent evidence suggests that the subthalamic nucleus (STN) is involved in regulating the incentive value of food reinforcers. The objective of this study was to examine the effect of lesions of the STN on intertemporal choice (choice between reinforcers differing in size and delay). Rats with bilateral quinolinic acid-induced lesions of the STN (n = 15) or sham lesions (n = 14) were trained in a discrete-trials progressive delay schedule to press levers A and B for a sucrose solution. Responses on A delivered 50 microl of the solution after a delay d(A); responses on B delivered 100 microl after a delay d(B). d(B) increased across blocks of trials; d(A) was manipulated across phases of the experiment. Indifference delay, d(B(50)) (value of d(B) corresponding to 50% choice of B), was estimated for each rat in each phase, and linear indifference functions (d(B(50)) vs. d(A)) were derived. The STN-lesioned group showed a flatter slope of the indifference function (implying higher instantaneous reinforcer values) than the sham-lesioned group; the intercepts did not differ between the groups. The results agree with recent evidence for a role of the STN in incentive value. Unlike some earlier studies, these results do not indicate a role of the STN in delay discounting.

Effects of lesions of the nucleus accumbens core on inter-temporal choice: further observations with an adjusting-delay procedure.

Previous experiments using progressive-delay schedules showed that destruction of the nucleus accumbens core (AcbC) altered rats' choice between food reinforcers differing in size and delay. Application of a quantitative model of inter-temporal choice suggested that lesions of the AcbC increase the delay-dependent degradation of reinforcer value (delay discounting) without altering instantaneous reinforcer value. This experiment examined the effect of lesions of the AcbC on inter-temporal choice using an adjusting-delay schedule. Rats received excitotoxin-induced lesions of the AcbC or sham lesions. They were trained to press levers A and B for food-pellet reinforcers in an adjusting-delay schedule in which the delay to the larger reinforcer, d(B), varied in accordance with the rats' choices between the two levers. In two experimental conditions, the reinforcers associated with levers A and B were 1 vs. 4 and 2 vs. 4 pellets. The AcbC-lesioned group showed shorter indifference delays to reinforcer B (d(B(50))) than the sham-lesioned group under both conditions. In confirmation of a prediction derived from the model of inter-temporal choice, the ratio of the indifference delays from the two conditions did not differ between the groups. Analysis of the cyclical changes in d(B) by Fourier transform showed that the period of oscillation and power within the dominant frequency band did not differ between the groups, suggesting that the lesion did not disrupt the rats' ability to detect short-term changes in delay of reinforcement. The results are consistent with previous findings that indicate a role for the AcbC in delay discounting.

Effect of reinforcer magnitude on performance maintained by progressive-ratio schedules.

This experiment examined the relationship between reinforcer magnitude and quantitative measures of performance on progressive-ratio schedules. Fifteen rats were trained under a progressive-ratio schedule in seven phases of the experiment in which the volume of a 0.6-M sucrose solution reinforcer was varied within the range 6-300 microl. Overall response rates in successive ratios conformed to a bitonic equation derived from Killeen's (1994) Mathematical Principles of Reinforcement. The "specific activation" parameter, a, which is presumed to reflect the incentive value of the reinforcer, was a monotonically increasing function of reinforcer volume; the "response time" parameter, delta, which defines the minimum response time, increased as a function of reinforcer volume; the "currency" parameter, beta, which is presumed to reflect the coupling of responses to the reinforcer, declined as a function of volume. Running response rate (response rate calculated after exclusion of the postreinforcement pause) decayed monotonically as a function of ratio size; the index of curvature of this function increased as a function of reinforcer volume. Postreinforcement pause increased as a function of ratio size. Estimates of a derived from overall response rates and postreinforcement pauses showed a modest positive correlation across conditions and between animals. Implications of the results for the quantification of reinforcer value and for the use of progressive-ratio schedules in behavioral neuroscience are discussed.

Attenuation of the effects of d-amphetamine on interval timing behavior by central 5-hydroxytryptamine depletion.

RATIONALE: Interval timing in the free-operant psychophysical procedure is sensitive to the monoamine-releasing agent d-amphetamine, the D(2)-like dopamine receptor agonist quinpirole, and the D(1)-like agonist 6-chloro-2,3,4,5-tetrahydro-1-phenyl-1H-3-benzepine (SKF-81297). The effect of d-amphetamine can be antagonized by selective D(1)-like and 5-HT(2A) receptor antagonists. It is not known whether d-amphetamine's effect requires an intact 5-hydroxytryptamine (5-HT) pathway. OBJECTIVE: The objective of this study was to examine the effects of d-amphetamine, quinpirole, and SKF-81297 on timing in intact rats and rats whose 5-hydroxytryptaminergic (5-HTergic) pathways had been ablated. MATERIALS AND METHODS: Rats were trained under the free-operant psychophysical procedure to press levers A and B in 50-s trials in which reinforcement was provided intermittently for responding on A in the first half, and B in the second half of the trial. Percent responding on B (%B) was recorded in successive 5-s epochs of the trials; logistic functions were fitted to the data for derivation of timing indices (T(50), time corresponding to %B = 50%; Weber fraction). The effects of d-amphetamine (0.4 mg kg(-1) i.p.), quinpirole (0.08 mg kg(-1) i.p.), and SKF-81297 (0.4 mg kg(-1) s.c.) were compared between intact rats and rats whose 5-HTergic pathways had been destroyed by intra-raphe injection of 5,7-dihydroxytryptamine. RESULTS: Quinpirole and SKF-81297 reduced T(50) in both groups; d-amphetamine reduced T(50) only in the sham-lesioned group. The lesion reduced 5-HT levels by 80%; catecholamine levels were not affected. CONCLUSIONS: d-Amphetamine's effect on performance in the free-operant psychophysical procedure requires an intact 5-HTergic system. 5-HT, possibly acting at 5-HT(2A) receptors, may play a 'permissive' role in dopamine release.

Effect of quinolinic acid-induced lesions of the subthalamic nucleus on performance on a progressive-ratio schedule of reinforcement: a quantitative analysis.

UNLABELLED: The subthalamic nucleus (STN), a major relay in the indirect striatofugal pathway, plays an important role in extrapyramidal motor control. Recent evidence indicates that it may also be involved in regulating the incentive value of food reinforcers. OBJECTIVE: To examine the effect of lesions of the STN on performance on a progressive-ratio schedule using a quantitative model that dissociates effects of interventions on motor and motivational processes [Killeen PR. Mathematical principles of reinforcement. Behav Brain Sci 1994;17:105-72]. Rats with bilateral quinolinic acid-induced lesions of the STN (n=14) or sham lesions (n=14) were trained to press a lever for food-pellet reinforcers under a progressive-ratio schedule. In Phase 1 (90 sessions) the reinforcer was one pellet; in Phase 2 (30 sessions) it was two pellets; in Phase 3 (30 sessions) it was again one pellet. RESULTS: The performance of both groups conformed to the model of progressive-ratio schedule performance. The motor parameter, delta, was significantly higher in the STN-lesioned than the sham-lesioned group, reflecting lower overall response rates in the lesioned group. The motivational parameter, a, was significantly higher in the STN-lesioned group than in the sham-lesioned group, consistent with enhanced reinforcer value in the STN-lesioned group compared to the sham-lesioned group. In both groups, a was sensitive to changes in reinforcer size, being significantly greater under the two-pellet condition (Phase 2) than under the one-pellet condition (Phases 1 and 3). The results suggest that destruction of the STN impairs response capacity and enhances the incentive value of food reinforcers.

Stroop performance in multiple sclerosis: information processing, selective attention, or executive functioning?

Cognitive impairments in information processing speed, attention and executive functioning are widely reported in patients with multiple sclerosis (MS). Several studies have identified impaired performance on the Stroop test in people with MS, yet uncertainty remains over the cause of this phenomenon. In this study, 25 patients with MS were assessed with a neuropsychological test battery including a computerized Stroop test and a computerized test of information processing speed, the Graded Conditional Discrimination Tasks (GCDT). The patient group was compared with an individually age, sex and estimated premorbid IQ-matched healthy control group. The patients' reaction times (RTs) were significantly longer than those of the controls on all Stroop test trials and there was a significantly enhanced absolute (RT(incongruent)-RT(neutral)) and relative (100 x [RT(incongruent)-RT(neutral)]/RT(neutral)) Stroop interference effect for the MS group. The linear function relating RT to stimulus complexity in the GCDT was significantly steeper in the patient group, indicating slowed information processing. The results are discussed with reference to the difference engine model, a theory of diversity in speeded cognition. It is concluded that, in the assessment of people with MS, great caution must be used in the interpretation of performance on neuropsychological tests which rely on RT as the primary measure.