Theoretical note: Quantity and concentration as co-determinants of the reinforcing value of sucrose: A re-analysis of some previously published data.

According to the Multiplicative Hyperbolic Model of reinforcer value (MHM), the overall value of a reinforcer may be defined by the multiplicative combination of a set of hyperbolic functions, each of which defines the impact of a particular feature of the reinforcer (e.g., quantity, immediacy of delivery). A previous experiment found that the relationship between the indifference volumes (qA(50)) of reinforcer A (a 0.4-M sucrose solution) and the fixed volume (qB) of reinforcer B (a 0.2-M sucrose solution: 32 - 256 µl) was consonant with this model. This paper describes a re-analysis of those data in an attempt to identify the nature of the effect of concentration on the two parameters of the size/value hyperbola (asymptote, ε, and sensitivity, Q). Comparison of two versions of the model in which (i) both parameters were free to vary as a function of qB and (ii) only ε was free to vary, showed that the latter model provided a satisfactory account of the data and that the inclusion of Q as an additional free parameter was not justified. Implications for the development of MHM are discussed.

Further observations on the reinforcing value of sucrose solutions: Interaction between quantity and concentration.

According to the Multiplicative Hyperbolic Model of reinforcer value (MHM), the value of a reinforcer is an increasing hyperbolic function of its size. In addition it is generally accepted that in the case of soluble reinforcers such as sucrose, value is an increasing function of molar concentration. The present experiment examined the interaction between size and concentration on the effectiveness of sucrose reinforcers in an operant choice paradigm. Rats were trained under an adjusting-magnitude schedule in which a response on lever B delivered a fixed volume of a sucrose solution, while a response on lever A delivered a 0.8-M sucrose solution, the volume of which, qA, was adjusted according to the rats' choices. When B was preferred in a given block of trials, qA was increased in the following block; when A was preferred, qA was reduced in the following block. The concentration and volume of B (cB, qB) were varied across six phases of the experiment and the corresponding indifference magnitudes of A (qA(50)) were measured. Log qA(50) increased and qB/qA(50) declined as approximately linear functions of log cB, consistent with the supposition that reinforcer value was determined by multiplicative combination of hyperbolic expressions representing concentration and volume.

The effect of adulteration with a bitter tastant, denatonium benzoate, on the reinforcing value of sucrose.

According to the Multiplicative Hyperbolic Model of reinforcer value (MHM), the value of a reinforcer is an increasing hyperbolic function of its size (q). A recent experiment examined the effect of adulterating a sucrose solution with citric acid on the value of a sucrose reinforcer. In contrast to expectations derived from MHM, the effect of citric acid was consistent with the summation of positive (sucrose) and negative (citric acid) values. The present experiment extended these observations to a bitter tastant, denatonium benzoate (DB). Rats were trained under an adjusting-magnitude schedule in which a response on lever B delivered a fixed volume of a sucrose/DB mixture, while a response on lever A delivered a sucrose solution, the volume of which, qA, was adjusted according to the rats' choices. When B was preferred in a given block of trials, qA was increased in the following block; when A was preferred, qA was reduced in the following block. qB was varied across five phases of the experiment and the corresponding indifference magnitudes of A were measured. The results indicated that, as was the case with citric acid, the value of the mixture reflected the summation of positive (sucrose) and negative (DB) values.

Adulteration of sucrose with citric acid: Effect on reinforcing value, examined using an adjusting-magnitude schedule of reinforcement.

According to the Multiplicative Hyperbolic Model (MHM), the value of a reinforcer is an increasing hyperbolic function of its size (q). Recently reported results indicated that dilution of a sucrose solution reduced its reinforcing value by increasing the 'size-sensitivity' parameter of this function and reducing its maximum. The present experiment examined whether adulterating a sucrose solution with citric acid would have a similar effect on the hyperbolic function. Rats were trained under an adjusting-magnitude schedule in which a response on lever B delivered a fixed volume of a sucrose/citric-acid mixture, while a response on lever A delivered a sucrose solution, the volume of which, qA, was adjusted according to the rats' choices. When B was preferred in a given block of trials, qA was increased in the following block; when A was preferred, qA was reduced in the following block. qB was varied across four phases of the experiment and the corresponding indifference magnitudes of A were measured. The results failed to support the hypothesis that adulteration with citric acid resulted in devaluation of sucrose. An alternative hypothesis derived from MHM, that the value of the mixture reflected the summation of positive (sucrose) and negative (citric acid) values, is discussed.

Choice between different concentrations of sucrose in an adjusting-magnitude schedule: Evidence for reinforcer-specific value maxima.

According to the Multiplicative Hyperbolic Model (MHM), an extension of Mazur's (1987) model of delay discounting, the value of a reinforcer is an increasing hyperbolic function of its size (q). This experiment tested a prediction based on a revised version of MHM (MHM-R), according to which the maximum value may differ between different reinforcers, a possibility not envisaged in MHM. Rats were trained under a discrete-trials adjusting-magnitude schedule in which a response on lever B delivered a dilute sucrose reinforcer (0.2 M) of fixed volume, qB, while a response on lever A delivered a more concentrated sucrose solution (0.4 M) the volume of which, qA, was adjusted according to the rats' choices. When B was preferred in a given block of trials, qA was increased in the following block; when A was preferred, qA was reduced in the following block. qB was varied across four phases of the experiment and the corresponding indifference magnitudes of A (qA(50)) were measured. In keeping with expectations based on both MHM and MHM-R, qA(50) increased approximately linearly with qB, and 1/qA(50) with 1/qB. The ratio qB/qA(50) increased linearly with qB with a positive intercept, a finding that is consistent with MHM-R but not with MHM.

In search of a definition of reinforcer value: Some successes and failures of the multiplicative hyperbolic model.

The concept of 'value' has enjoyed a central position in many theoretical accounts of choice behaviour. Several definitions of 'value' are contrasted in this paper, and one particular approach is defended, whereby value is defined as a dimensionless intervening variable. This definition is a cornerstone of the multiplicative hyperbolic model of choice (MHM), which was proposed twenty years ago as a modification of Mazur's (1987) hyperbolic model of delay discounting. This paper reviews some of the merits and shortcomings of MHM, and suggests some ways in which MHM might be extended and improved. A formal link between 'value' and the related concept of 'response strength' is suggested, and revisions of the model are proposed which may enable it to accommodate several behavioural phenomena not considered in the original formulation. Broadening the scope of MHM comes at the cost of adding to its burden of free parameters, and it is emphasised that addition of any new parameters needs empirical justification. The status of value as a dimensionless intervening variable is upheld; however it is noted that a growing body of empirical evidence for links between neurobiological phenomena and value suggests that interpretation of value as a hypothetical construct may be warranted.

Effects of sucrose concentration on choice in an adjusting-magnitude schedule.

Rats were trained under a discrete-trials adjusting-magnitude schedule in which a response on lever A delivered either a larger or a smaller sucrose reinforcer (qA1 = 8 µl, qA2 = 64 µl) with equal probability, while a response on B delivered a reinforcer whose size qB was adjusted according to the rats' choices. When A was preferred in a given block of trials, qB was increased in the following block; when B was preferred, qB was reduced in the following block. The oscillating changes in qB, analysed by the Fourier transform, could be described by a power spectrum whose dominant frequency corresponded to a period of 40-50 trial blocks. The equilibrium value of qB (qB(50)) was inversely related to sucrose concentration; it significantly exceeded the arithmetic mean of qA1 and qA2 when the concentration was 0.2 or 0.4 M, but not when it was 0.8 or 1.6 M. Analysis by mixed-effects modelling revealed a trend for the power of oscillation of qB to increase monotonically with sucrose concentration; the period of oscillation was not systematically related to sucrose concentration. These results are consistent with predictions derived from a revised version of the multiplicative hyperbolic model of intertemporal choice.

Some properties of an adjusting-magnitude schedule of reinforcement: Implications for models of choice.

Rats were trained under a discrete-trials adjusting-magnitude schedule in which a response on lever A delivered either a larger or a smaller reinforcer (qA1 and qA2) with equal probability, while a response on B delivered a reinforcer whose size qB was adjusted according to the rats' choices. When A was preferred in a given block of trials, qB was increased in the following block; when B was preferred, qB was reduced in the following block. The oscillating changes in qB, analysed by the Fourier transform, could be described by a power spectrum with a dominant period of about 50 trial blocks. With qA1 held constant, the equilibrium value of qB (qB(50)) was monotonically related to qA2, and exceeded the arithmetic mean of qA1 and qA2 when qA1 was substantially greater than qA2. A model derived from the multiplicative model of intertemporal choice provided a post hoc description of the data. Simulation of block-by-block changes in qB derived from the model were generally consistent with the experimental data. Implications of the results for models of risky choice and for future use of the schedule in neurobehavioural experiments are discussed.

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.

Effect of streptozotocin-induced diabetes on performance on a progressive ratio schedule.

RATIONALE: It has been suggested that streptozotocin (STZ)-induced diabetes causes a motivational deficit in rodents. However, some of the evidence adduced in support of this suggestion may be interpreted in terms of a motor impairment rather than a motivational deficit. OBJECTIVE: This experiment examined the effect of STZ-induced diabetes on performance on a progressive ratio schedule. The data were analysed using a new model derived from Killeen's (Behav Brain Sci 17:105-172, 1994) Mathematical Principles of Reinforcement model which enables the effects of interventions on motivation or incentive value to be separated from effects on motor function. METHOD: Animals were trained under a progressive ratio schedule using food-pellet reinforcement. Then they received a single intraperitoneal injection of 50 mg/kg of STZ or the vehicle. Training continued for 30 sessions after 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 groups. RESULTS: The parameter expressing incentive value was reduced in the group treated with STZ, whereas the parameters expressing motor capacity and post-reinforcement pausing were not affected by the treatment. Blood glucose concentration was significantly elevated in the STZ-treated group compared to the vehicle-treated group. CONCLUSIONS: The results are consistent with the suggestion that STZ-induced diabetes is associated with a reduction of the incentive value of food.

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.

A theory of behaviour on progressive ratio schedules, with applications in behavioural pharmacology.

RATIONALE: Mathematical principles of reinforcement (MPR) provide the theoretical basis for a family of models of schedule-controlled behaviour. A model of fixed-ratio schedule performance that was applied to behaviour on progressive ratio (PR) schedules showed systematic departures from the data. OBJECTIVE: This study aims to derive a new model from MPR that will account for overall and running response rates in the component ratios of PR schedules, and their decline toward 0, the breakpoint. METHOD: The role of pausing is represented in a real-time model containing four parameters: T (0) and k are the intercept and slope of the linear relation between post-reinforcement pause duration and the prior inter-reinforcer interval; a (specific activation) measures the incentive value of the reinforcer; δ (response time) sets biomechanical limits on response rate. Running rate is predicted to decrease with negative acceleration as ratio size increments, overall rate to increase and then decrease. Differences due to type of progression are explained as hysteresis in the control by reinforcement rates. Re-analysis of extant data focuses on the effects of acute treatment with antipsychotic drugs, lesions of the nucleus accumbens core, and destruction of orexinergic neurones of the lateral hypothalamus. RESULTS: The new model resolves some anomalies evident in earlier analyses, and provides new insights to the results of these interventions. CONCLUSIONS: Because they can render biologically relevant parameters, mathematical models can provide greater power in interpreting the effects of interventions on the processes underlying schedule-controlled behaviour than is possible for first-order data such as the breakpoint.

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.