Stanley J. Weiss

Cocaine self-administration increased by compounding discriminative stimuli

Presenting independently established discriminative stimuli in compound can substantially increase response rates under food and shock-avoidance schedules. To determine whether this effect extends to drug self-administration, rats were trained to press a lever to receive cocaine intravenously. A tone and a light were independently established as discriminative stimuli for cocaine self-administration, then presented in combination in a stimulus-compounding test. Compared to tone and light alone, the tone-plus-light compound stimulus increased responding approximately three-fold when cocaine was withheld during testing, and it increased drug intake approximately two-fold when cocaine was made available during testing. Compounding did not increase responding after training in a truly random control condition where tone and light were presented uncorrelated with the availability of cocaine. The results obtained with this animal model of drug abuse define conditions under which combinations of environmental stimuli might substantially increase human drug use.

Sign-tracking (autoshaping) in rats: A comparison of cocaine and food as unconditioned stimuli

A series of experiments was performed to determine whether sign-tracking would occur in rats with intravenous (i.v.) cocaine as the unconditioned stimulus. In Experiment 1, a retractable lever paired with food produced strong sign-tracking, but a lever paired with one of three doses of i.v. cocaine did not elicit any approach or contact behavior. Experiment 2 demonstrated that doses of cocaine that did not elicit sign-tracking would function as a positive reinforcer for a lever contact operant. In Experiment 3, an artificialconsummatory response was added to make the cocaine reinforcement episode more behaviorally comparable to that occasioned by food. Although the rats readily performed this response when it was required to receive cocaine infusions, they still did not contact a lever that signaled the availability of these infusions. It appears that cocaine is different from other positive reinforcers (e.g., food, water, warmth, or intracranial stimulation) in that it will not produce sign-tracking in rats.

A comparison of Lewis and Fischer rat strains on autoshaping (sign-tracking), discrimination reversal learning and negative automaintenance

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.

Conditioned inhibition of cocaine seeking in rats.

Despite its potential relevance to the treatment of drug abuse, conditioned inhibition of drug seeking has not been systematically investigated before. In this study, rats could self-administer cocaine by lever pressing whenever a click or tone was present. Responding was not reinforced when a light was present. The light was presented simultaneously with the click (i.e., in an excitatory context) in 1 group, but the light was always presented alone in another group. When it was later presented in compound with the tone, the light was a highly effective conditioned inhibitor, suppressing cocaine seeking by 92% in the former group and by 74% in the latter. These results suggest ways to improve cue-oriented behavioral treatments for drug abuse.

The influence of positive and negative reinforcement on selective attention in the rat

In Experiments 1 and 2 rats were trained under two multiple schedules of reinforcement. In one, bar pressing during a tone-light compound stimulus was reinforced under a variable-interval food reinforcement schedule. In the other multiple schedule, bar pressing avoided grid shock on a free-operant schedule. In both multiple schedules, a discrimination was maintained by an extinction schedule that was operative during the absence of the tone-light compound. In Experiments 1 and 2 the intensity of the tone-light compound was manipulated over three levels. Subsequent extinction tests revealed that light was attended to, almost exclusively of the tone, when food reinforcement had maintained bar pressing. On the other hand, the tone gained considerable attentional control under the shock avoidance schedule. This stimulus-reinforcer interaction was maintained for all three levels of the compound intensity. In Experiment 3 it was investigated whether this interaction was associative by presenting shock during the absence of the tone-light compound when food reinforcement maintained responding, and food during the absence of the compound when shock avoidance maintained responding. Since both food and shock were presented during a single session for both schedules, nonassociative effects of the reinforcing stimuli were equivalent across the schedules. Nevertheless, the stimulus-reinforcer interaction was maintained, indicating that the interaction was an associative effect.

Stimulus control of free-operant avoidance: The contribution of response rate and incentive relations between multiple-schedule components

Abstract The associations formed in the components of a multiple schedule can be classified as (1) stimulus-response (S-R) associations and (2) stimulus-reinforcer (S-S R ) associations. The present experiments sought to determine the individual contribution of these S-R and S-S R associations to stimulus control by manipulating them independently. Responses postponed shocks by 25 sec in the presence of a tone alone and a light alone in all experiments. The contingencies programmed in the absence of both tone and light established a reference for the S-R and S-S R associations in tone and in light. All four possible combinations of signalling response increase or decrease together with incentive increase or decrease were studied. Although the influence of the contingencies operating in the absence of tone and light was difficult to detect from response rates in tone or light, presenting tone and light together revealed clear effects. Response rates in tone and light together relative to those in either alone depended upon the contingency operating in the absence of tone and light. Stimulus-response and stimulus-reinforcer associations appeared to counteract each other when in opposition and combine together to enhance each other when in agreement. This suggested that the associations of a stimulus to response and to incentive combine algebraically in determining stimulus control. An algebraic analysis in terms of the S-R and S-S R associations conditioned to the stimulus elements comprising the training and test stimuli accounted for the observed patterns of data.

Conditioned suppression of behavior maintained by cocaine self-administration

Shock-paired stimuli have produced conditioned suppression of behavior maintained by a variety of reinforcers such as food, water, sucrose, and intracranial self-stimulation. With the ongoing pursuit of animal models for drug abuse treatment, it is surprising that this procedure for suppressing positively reinforced behavior has never been applied to drug-maintained behavior. The present study applied the conditioned suppression paradigm to behavior maintained by cocaine self-administration in rats. If shock-paired stimuli suppress ongoing cocaine self-administration, this would contrast with recent studies reporting that aversive stimuli can enhance the acquisition and reinstatement of behavior reinforced by cocaine. Rats were trained to bar-press for intravenous cocaine infusions on a variable-interval schedule. Then, a tone conditioned stimulus (CS) and a light CS were each paired with foot-shock while the rats were bar-pressing for cocaine. These CSs each came to reliably suppress responding in all subjects, just as shock-paired CSs suppressed responding by the positive reinforcers mentioned above. When the tone and the light were presented simultaneously in testing, suppression was significantly enhanced over that controlled by the single CSs. These results demonstrate that (1) cocaine-maintained behavior can be suppressed by environmental stimuli associated with non-drug reinforcers; and (2) combining stimuli that decrease drug self-administration can enhance their suppressive effects. Thus, the present findings can have implications for drug treatment.

Deepened Extinction of Cocaine Cues

BACKGROUND A method for reducing the power of drug cues could help in treating drug abuse and addiction. Extinction has been used, with mixed success, in such an effort. Research with non-drug cues has shown that simultaneously presenting (compounding) those cues during extinction can enhance the effectiveness of extinction. The present study investigated whether this procedure could be used to similarly deepen the extinction of cocaine cues. METHODS Rats were first trained to self-administer cocaine during tone, click, and light stimuli. Then, these stimuli were subjected to extinction in an initial phase where they were presented individually. In a second extinction phase, one of the auditory stimuli (counterbalanced) was compounded with the light. The other auditory stimulus continued to be presented alone. Rats were then given a week of rest in their homecages prior to testing for spontaneous recovery of cocaine seeking. RESULTS The cue that was compounded with the light during the second phase of extinction training occasioned less spontaneous recovery of cocaine seeking than the cue that was always presented individually during extinction. Increasing the number of compound cue extinction sessions did not produce a greater deepened extinction effect. CONCLUSIONS The present study showed that simultaneously presenting already-extinguished cocaine cues during additional extinction training enhanced extinction. This extends the deepened extinction effect from non-drug cues to drug cues and further confirms predictions of error-correction learning theory. Incorporating deepened extinction into extinction-based drug abuse treatments could help to reduce the power of drug cues.

Learning that a cocaine reward is smaller than expected: A test of Redish's computational model of addiction

The present experiment tested the prediction of Redishs (2004) computational model of addiction that drug reward expectation continues to grow even when the received drug reward is smaller than expected. Initially, rats were trained to press two levers, each associated with a large dose of cocaine. Then, the dose associated with one of the levers was substantially reduced. Thus, when rats first pressed the reduced-dose lever, they expected a large cocaine reward, but received a small one. On subsequent choice tests, preference for the reduced-dose lever was reduced, demonstrating that rats learned to devalue the reduced-dose lever. The finding that rats learned to lower reward expectation when they received a smaller-than-expected cocaine reward is in opposition to the hypothesis that drug reinforcers produce a perpetual and non-correctable positive prediction error that causes the learned value of drug rewards to continually grow. Instead, the present results suggest that standard error-correction learning rules apply even to drug reinforcers.

Motivational effects of compounding discriminative stimuli associated with food and cocaine

Abstract In previous experiments, the compounding of two discriminative stimuli associated with the same reinforcer increased rats’ responding approximately three-fold, regardless of whether the reinforcer was food, water, cocaine, or shock-avoidance. Compounding a discriminative stimulus associated with food with one associated with water increased responding two-fold. In the present experiment, compounding a discriminative stimulus associated with food with one associated with cocaine increased responding two-fold. These results support the hypothesis that 1) the effects of stimuli associated with reinforcers from the same incentive class (appetitive or aversive) are mutually enhancing, and 2) the combined effects of stimuli associated with two different reinforcers from within the same class are not as strong as those of two stimuli associated with the same reinforcer. These results also suggest that discriminative stimuli associated with non-drug reinforcers may increase the motivation to self-administer cocaine when encountered in combination with drug-related stimuli.