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Background: Previous research with non-drug reinforcers has shown that simultaneously presenting (compounding) an extinguished cue with another cue formerly associated with the same reinforcer can increase rates of cue-controlled behavior. The present study investigated whether an extinguished cocaine cue would energize cocaine seeking when presented simultaneously with another cocaine cue. This study also investigated whether extinction could be enhanced by subjecting an extinguished cocaine cue to further extinction after administration of reinstating injections of cocaine., Methods: Rats were first trained to self-administer cocaine in the presence of three different cues. Then, one of the cues was subjected to the standard extinction treatment. Another cue was subjected to a modified extinction treatment where additional extinction sessions were preceded by non-contingent cocaine injections. The third cue was not extinguished., Results: The cue subjected to standard extinction ceased to control cocaine seeking when presented alone, but significantly increased cocaine seeking when compounded with the non-extinguished cocaine cue. The cocaine cue subjected to the modified extinction treatment also significantly increased cocaine seeking occasioned by the non-extinguished cocaine cue., Conclusions: Extending results of previous studies involving non-drug stimuli, the present study showed that extinguished cocaine cues can enhance cocaine seeking when compounded with other cocaine cues. These results illustrate the persistence of drug cues in controlling behavior despite extinction and highlight the need for developing treatments that eliminate this residual energizing capacity that survives extinction., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

According to the composite-stimulus control model (Weiss, 1969, 1972b), an individual discriminative stimulus (S(D)) is composed of that S(D)'s on-state plus the off-states of all other relevant S(D)s. The present experiment investigated the reversibility of composite-stimulus control. Separate groups of rats were trained to lever-press for food whenever a tone or a light S(D) was present. For one group, the nonreinforced S(Delta) condition was tone-and-light absence (T+L). Tone-plus-light (T+L) was S(Delta) in the other group. On a "stimulus compounding" test that recombined composite elements, maximum responding occurred to that composite consisting only of elements occasioning response increase. That was T+L for the group trained with T+L as S(Delta) and T+L for the group trained with T+L as S(Delta). The S(Delta) composite was next reversed over groups in Phase 2. In Phase 2 tests, maximum responding that was comparable in magnitude to that of Phase 1 was again controlled by the composite consisting only of elements most recently occasioning response increase-whether T+L or T+L. The inhibitory conditioning history of both composite-elements currently occasioning responding did not weaken the summative effect. These results confirm and extend Weiss's composite-stimulus control model, and demonstrate that such control is fully reversible. We discuss how translating conditions of the stimulus-compounding paradigm to a composite continuum creates a functional and logical connection to intradimensional control measured through stimulus generalization, reducing the number of different behavioral phenomena requiring unique explanations.

In two experiments, the effects of Pavlovian or discriminative conditioned inhibitors on operant responding were investigated in rats. Experiment 1 found that a Pavlovian conditioned inhibitor for food suppressed food-reinforced lever pressing more than a non-differentially trained control stimulus did. Experiment 2 demonstrated that an operant discriminative inhibitor produced greater suppression of lever pressing than a Pavlovian conditioned inhibitor. Experiment 2 also found that compounding an operant discriminative stimulus (SD) for food-reinforced responding with another SD for food-reinforced responding resulted in more additive summation than when an SD was compounded with a Pavlovian conditioned excitor for food. The results of these experiments support two-factor theories that postulate that incentive and response discriminative processes summate algebraically when the processes are inhibitory or excitatory.

The present experiment investigated contextual renewal of cocaine seeking and potential methods of attenuating this renewal. Rats were first trained in one context to self-administer cocaine when a discriminative stimulus (tone) was presented. Then, the ABA Group was placed in a second context and responses in tone no longer produced cocaine (extinction). The AAA Group received this extinction in the original context. For two additional groups, responding to the tone was eliminated in a second context by additionally presenting food in tone according to a differential-reinforcement-of-other-behavior (DRO Group) schedule or independently of the rats' behavior on a fixed-time (FT Group) schedule. Renewal of responding to the tone was observed when the ABA Group was returned to the original context for a renewal test, but no renewal was observed in the AAA Group. Renewal also occurred in the DRO and FT Groups upon returning to the original context, but this renewal was significantly less than that of the ABA Group. These results suggest that response elimination techniques that are more active than simple extinction, such as pairing drug-related stimuli with alternative reinforcement, could reduce renewal of drug seeking and thereby help prevent relapse.

Previous experiments have demonstrated that the simultaneous presentation of independently established discriminative stimuli can control rates of operant responding substantially higher than the rates occasioned by the individual stimuli. This "additive summation" phenomenon has been shown with a variety of different reinforcers (e.g., food, water, shock avoidance, cocaine, and heroin). Discriminative stimuli previously used in such studies have been limited to the visual and auditory sensory modalities. The present experiment sought to (1) establish stimulus control on a free-operant baseline with an ambient olfactory discriminative stimulus, (2) compare olfactory control to that produced with an auditory discriminative stimulus, and (3) determine whether compounding independently established olfactory and auditory discriminative stimuli produces additive summation. Rats lever pressed for food on a variable-interval schedule in the presence of either a tone or an odor, with comparable control developed to each stimulus. In the absence of these stimuli responding was not reinforced. During stimulus compounding tests, the tone-plus-odor compound occasioned more than double the responses occasioned by either the tone or odor presented individually. Thus, the current study (1) established stimulus control with an ambient olfactory discriminative stimulus in a traditional free-operant setting and (2) extended the generality of stimulus-compounding effects by demonstrating additive summation when olfactory and auditory discriminative stimuli were presented simultaneously.

Lewis (LEW) and Fischer (F344) rat strains differ on a number of physiological characteristics, such as hypothalamic-pituitary-adrenal (HPA) axis activity, as well as on behavioral tasks, including those that measure impulsivity and drug reward. Since autoshaping, the phenomenon where animals approach and contact reward-paired conditioned stimuli, has been linked to HPA axis functioning, impulsivity and drug taking, the present study compared LEW and F344 rats on the rate of acquisition and performance of the autoshaping response. Rats were trained on an autoshaping procedure where insertions of one retractable lever (CS(+)) were paired response-independently with food, while insertions of another lever (CS(-)) were not paired with food. LEW rats acquired the autoshaping response more rapidly and also performed the autoshaping response at a higher rate than F344 rats. No differences between the strains were observed when rats were trained on a discrimination reversal where the CS(+) and CS(-) levers were reversed or during a negative auto-maintenance phase where CS(+) lever contacts cancelled food delivery. Potential physiological mechanisms that might mediate the present results, including strain differences in HPA axis and monoamine neurotransmitter activity, are discussed. The finding that LEW (as compared to F344 rats) more readily acquire autoshaping and perform more responses is consistent with research indicating that LEW rats behave more impulsively and more readily self-administer drugs of abuse.

After a tone and a light were established as discriminative stimuli for food-reinforced responding in rats, presenting these stimuli simultaneously produced over three times as many responses as either the tone or light alone. Following this stimulus compounding test, responses during the tone and during the light were not reinforced (extinction) for 20 sessions, essentially eliminating responding. On stimulus compounding tests administered after the 10th and 20th extinction sessions, tone-plus-light continued to produce significantly more responding than the tone or light alone. The compound even produced responses when the individual stimuli no longer did. These results suggest that the simultaneous presentation of multiple extinguished discriminative stimuli may also contribute to the reinstatement of other positively-reinforced behaviors, such as drug taking.

When 2 stimuli that occasion cocaine self-administration are presented in compound, their ability to increase cocaine-reinforced operant responding is substantially enhanced. The goal of the present experiment was to determine whether stimulus compounding could produce analogous enhancements of a classically conditioned drug effect. Food-maintained responding in rats was suppressed by a tone and a light that were individually paired with response-independent cocaine (3 mg/kg iv). This conditioned suppression was significantly enhanced when the stimuli were presented together in a stimulus-compounding test. The magnitude of this enhancement was similar to that in previous studies in which responding was suppressed by shock-paired stimuli. These results demonstrate that multiple drug-related cues interact in a predictable manner to influence both operant and classically conditioned behavior.

The dynamics of appetitive-aversive interaction theory were assayed in an experiment where excitors and inhibitors from the same and different incentive classes were compounded. Excitatory and inhibitory incentive properties acquired by the discriminative stimuli resulted from the reinforcement differences between components of four-component multiple training schedules, with the influence of competing peripheral responses factored into the design. Rats' barpressing was maintained in tone and in click by food or free-operant shock avoidance; extinction was programmed in click-plus-light and in the simultaneous absence of tone, click, and light. In Test 1, an excitor that occasioned operant responding and an inhibitor that occasioned response cessation were compounded. Here, compounding an inhibitor with an excitor from the same incentive class reduced responding significantly more than did compounding an inhibitor with an excitor from the other incentive class. In Test 2, the compounds consisted of elements that individually occasioned operant responding. Here, compounding stimuli that were excitors from different incentive classes appeared to create reciprocal inhibition that counteracted the additive effects produced when these stimuli were excitors from the same incentive class. Predictions from appetitive-aversive interaction theory and Weiss' two-factor model of stimulus control were confirmed within this experimental design, where all conditioning was a by-product of the behavioural contingencies programmed on the operant baselines.

Rats were trained to press a lever in the presence of a tone-light compound stimulus and not to press in its absence. In each of two experiments, schedules were designed to make the compound a conditioned punisher for one group and a conditioned reinforcer for the other. In Experiment 1, one group's responding produced food in the presence of the compound but not in its absence. The other group's responding terminated the compound stimulus, and food was presented only in its absence. When tone and light were later presented separately, light controlled more responding than did tone in the former group, but tone gained substantial control in the latter. The same effects were also observed within subjects when the training schedules were switched over groups. In Experiment 2, two groups avoided shock in the presence of the compound stimulus. In the absence of the compound, one group was not shocked, and the other received both response-independent and response-produced shock. When tone and light were presented separately, the former group's responding was mainly controlled by tone, but the latter group's responding was almost exclusively controlled by light. These effects were also observed within subjects when the training schedules were switched over groups. Thus, these single-incentive selective association effects (appetitive in Experiment 1 and aversive in Experiment 2) were completely reversible. The schedules in which the compound should have been a conditioned reinforcer consistently produced visual control, and auditory control increased when the compound should have become a conditioned punisher. Currently accepted accounts of selective associations based on affinities between shock and auditory stimuli and between food and visual stimuli (i.e., stimulus-reinforcer interactions) do not adequately address these results. The contingencies of reinforcement most recently associated with the compound and with its absence, rather than the nature of the reinforcer, determined whether auditory or visual stimulus control developed.

Pigeons acquired discriminated key pecking between 528- and 540-nm stimuli by either a response-reinforcer (operant group) or a stimulus-reinforcer (autoshaped group) contingency, with other training-schedule parameters comparable over groups. For the birds in the operant group, key pecks intermittently produced grain in the presence of one hue on the key (positive stimulus) but not in the other (negative stimulus). For the birds in the autoshaped group, pecking emerged when grain was intermittently presented independently of key pecking during one key color but was not presented during the other key color. Two independent contingency assays, peck-location comparisons and elimination of differences in reinforcement rate, confirmed the effectiveness of the two training procedures in establishing operant or respondent control of key pecking. After reaching a 10:1, or better, discrimination ratio between key pecks during the two key colors, the birds received a wavelength generalization test. Criterion baseline key-peck rates were comparable for operant and autoshaped groups prior to testing. On the generalization test, performed in extinction, all birds pecked most at a stimulus removed from the positive training stimulus in the direction away from the negative stimulus. In testing, autoshaped "peak" rates (24.5 to 64.9 pecks per minute) were from 33% to 80% higher than rates in the presence of the training stimuli. Respondent peak shift rarely has been reported heretofore, and never this consistently and robustly. These results further confirm the similarity of perceptual processing in classical and operant learning. They are discussed in terms of Spence's gradient-interaction theory and Weiss' (1978) two-process model of stimulus control.

Previous work (Thomas et al. 1990) showed that an anxiolytic benzodiazepine increased the time allocated to responding in a conflict situation (where responses were both food-reinforced and shock-punished) versus a nonpunishment situation. The present experiment tested whether a benzodiazepine-receptor inverse agonist (FG 7142, 1-30 mg/kg) would have the opposite effect (i.e., decrease time spent responding in a punishment situation). Chain pulls determined whether a rat's lever presses were reinforced on 1) a lean variable-interval schedule, or 2) a richer variable-interval schedule in which responding also produced shock intermittently. FG 7142 dose-dependently decreased nonpunished lever responding, but did not affect punished responding. The drug nonselectively decreased chain pulling (the schedule-switching response). Like chlordiazepoxide, FG 7142 increased the time spent in the punishment component, showing that not all effects of benzodiazepine-receptor agonists and inverse agonists are opposite. These results are inconsistent with expectations that anxiogenic actions of FG 7142 should 1) decrease punished responding; 2) increase the rate of responses that terminate the punishment condition; and 3) decrease time spent in the punishment component. Rather, nonsuppressed responding seems most sensitive to decreases by FG 7142.

Instrumental treadle press and nonreinforced key peck responses were monitored during discrimination training and generalization testing in pigeons on positive and negative reinforcement schedules. In Experiment 1, six pigeons pressed a treadle for food on a multiple variable-interval extinction schedule. In Experiment 2, three pigeons pressed a treadle to avoid shock on a multiple free-operant avoidance extinction schedule. Different color keylights signaled S+ and S- components. Some positive behavioral contrast occurred during discrimination training, but the effect was small. Pecking occurred to the S+ keylight in Experiment 1 but not in Experiment 2. On stimulus generalization tests, all subjects displayed a positive peak shift when pressing the treadle for food or to avoid shock. However, peak shift was not found for nonreinforced "autopecks" on the stimulus key, although an area shift was observed in Experiment 1. This is the first demonstration of peak shift for pigeons pressing treadles and the only reliable demonstration of peak shift when negative reinforcement maintained responding. These results, in combination with previous demonstrations of peak shift for rats pressing levers and pigeons pecking keys, indicate that peak shift is a general by-product of operant discrimination learning, since it occurs across a variety of the organisms, responses, and reinforcers.

In Experiment 1, a light and a tone were correlated independently with water reinforcement of bar pressing by rats. With different naive subjects in Experiment 2, one of these stimuli was correlated with food and the other with water reinforcement (counterbalanced). In both experiments the absence of tone and light signaled extinction. Tests of stimulus-reinforcer independence in Experiment 2 indicated that tone and light controlled behavior whose rate was specifically affected by deprivation state. In the stimulus-compounding tests of both experiments, response rates were higher to tone-plus-light than to tone or light presented alone (additive summation). This is the first report of additive summation produced through compounding stimuli paired with different reinforcers. The results are discussed in the context of the effects of incentive motivation on operant performance.

Four rats were trained on a schedule containing stimuli associated with variable-interval 30-sec and differential-reinforcement-of-low-rate 20-sec schedules of reinforcement. Subsequently, a stimulus compounding test was administered that included individual presentations of two intensities of each stimulus plus compounds of these stimuli. In training, extremely high rates were emitted to the variable-interval stimulus, and very low rates to the differential-reinforcement-of-low-rate stimulus. Compounding the two training stimuli always produced an overall response rate intermediate between the rates controlled by the two stimuli separately presented. Essentially the same relationship held with different stimulus intensities. These results resolve the confounding of response and reinforcement variables present in previous conditioning studies reporting response averaging. They are discussed in terms of the incompatibility of the response chains associated with the individual stimuli compounded.