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PubMed2005

Selective dopamine D3 receptor antagonism by SB-277011A attenuates cocaine reinforcement as assessed by progressive-ratio and variable-cost-variable-payoff fixed-ratio cocaine self-administration in rats.

In rats, acute administration of SB-277011A, a highly selective dopamine (DA) D(3) receptor antagonist, blocks cocaine-enhanced brain stimulation reward, cocaine-seeking behaviour and reinstatement of cocaine-seeking behaviour. Here, we investigated whether SB-277011A attenuates cocaine reinforcement as assessed by cocaine self-administration under variable-cost-variable-payoff fixed-ratio (FR) and progressive-ratio (PR) reinforcement schedules. Acute i.p. administration of SB-277011A (3-24 mg/kg) did not significantly alter cocaine (0.75 mg/kg/infusion) self-administration reinforced under FR1 (one lever press for one cocaine infusion) conditions. However, acute administration of SB-277011A (24 mg/kg, i.p.) progressively attenuated cocaine self-administration when: (a) the unit dose of self-administered cocaine was lowered from 0.75 to 0.125-0.5 mg/kg, and (b) the work demand for cocaine reinforcement was increased from FR1 to FR10. Under PR (increasing number of lever presses for each successive cocaine infusion) cocaine reinforcement, acute administration of SB-277011A (6-24 mg/kg i.p.) lowered the PR break point for cocaine self-administration in a dose-dependent manner. The reduction in the cocaine (0.25-1.0 mg/kg) dose-response break-point curve produced by 24 mg/kg SB-277011A is consistent with a reduction in cocaine's reinforcing efficacy. When substituted for cocaine, SB-277011A alone did not sustain self-administration behaviour. In contrast with the mixed DA D(2)/D(3) receptor antagonist haloperidol (1 mg/kg), SB-277011A (3, 12 or 24 mg/kg) failed to impede locomotor activity, failed to impair rearing behaviour, failed to produce catalepsy and failed to impair rotarod performance. These results show that SB-277011A significantly inhibits acute cocaine-induced reinforcement except at high cocaine doses and low work requirement for cocaine. If these results extrapolate to humans, SB-277011A or similar selective DA D(3) receptor antagonists may be useful in the treatment of cocaine addiction.

Animals↗

PubMed2006

Operant responding for conditioned and unconditioned reinforcers in rats is differentially enhanced by the primary reinforcing and reinforcement-enhancing effects of nicotine.

RATIONALE: Nicotine self-administration in rats is modest when response-contingent nicotine infusions are delivered alone (primary reinforcement) but robust when nicotine infusions are combined with a mildly reinforcing non-pharmacological stimulus. Furthermore, response-independent (non-contingent) nicotine administration also elevates responding for that same non-pharmacological stimulus, suggesting that in addition to primary reinforcement, nicotine can enhance the incentive value of other reinforcers. OBJECTIVES: In this study, we tested the hypothesis that the reinforcement-enhancing effects of non-contingent nicotine are more dependent on the reinforcing strength of the non-pharmacological stimulus than are the effects of contingent nicotine. MATERIALS AND METHODS: A weakly reinforcing light-tone stimulus was established as a conditioned reinforcer by repeated pairings with sucrose for some rats, or by delivery in an explicitly unpaired design with sucrose to other rats. Subsequently, both groups lever pressed for the stimulus with contingent nicotine, non-contingent nicotine (0.06 mg kg(-1) per infusion, freebase), or non-contingent saline, according to fixed ratio and progressive ratio reinforcement schedules. RESULTS: Compared to sucrose-unpaired training, repeated association with sucrose established the light-tone stimulus as a robust conditioned reinforcer. Contingent and non-contingent nicotine equally elevated responding for this conditioned stimulus. Conversely, for the less reinforcing (sucrose-unpaired) stimulus contingent nicotine more effectively elevated behavior compared to non-contingent nicotine. CONCLUSIONS: The reinforcement-enhancing effect of nicotine increases behavior controlled by both conditioned and unconditioned reinforcers; however, for less salient stimuli associative processes derived from the primary reinforcing effects of contingent nicotine may also be important. These data suggest that nicotine present in tobacco may differentially modulate stimulus-driven behavior in smokers.

Animals↗

PubMed1984

Hippocampus, time, and memory.

Five experiments were conducted to determine the effects of hippocampal damage on timing and the memory for temporal events. In Experiments 1-3, rats were trained to discriminate between auditory signals that differed in both duration (2 or 8 s) and rate (2 or 16 cycles/s). Half of the rats were trained to discriminate duration, and half were trained to discriminate rate. After rats acquired the relevant discrimination, signals with intermediate durations and rates were presented to obtain psychophysical functions that related signal duration and/or rate to response choice. Rats then received either lesions of the fimbria-fornix or control operations. Postoperatively, the accuracy of duration and rate discriminations as measured by the difference limen (DL) was unaffected by the lesion, but the point of subjective equality (PSE) was shifted to a shorter duration and a slower rate by the lesion in Experiment 1. Both rats with lesions and rats with control operations showed cross-modal transfer of duration and rate from the auditory signals used in training to visual signals used in testing in Experiment 2. A 5-s delay was imposed between the end of a signal and the opportunity to respond in Experiment 3. The delay served as a retention interval for the rats trained in the rate discrimination, and the rats with fimbria-fornix lesions were selectively impaired by the addition of the delay as measured by an increase in the DL. The delay did not serve as a retention interval for rats trained in the duration discrimination because they were able to continue timing through the delay. A peak procedure was employed in Experiment 4. The maximum response rate of control rats was approximately at the time of scheduled reinforcement (20 s), but the maximum response rate of rats with fimbria-fornix lesions was reliably earlier than the time of scheduled reinforcement. When a 5-s gap was imposed in the signal, control rats summed the signal durations before and after the gap, whereas rats with fimbria-fornix lesions showed no retention of the signal duration prior to the gap. Experiment 5 continued the testing of the rats used in Experiments 1-4 and showed that rats with lesions had an impairment in a test of spatial working memory in an eight-arm radial maze. Taken together, these results demonstrate that a fimbria-fornix lesion interferes with temporal and spatial working memory, reduces the remembered time of reinforcement stored in reference memory, and has no effect on the animal's sensitivity to stimulus duration.

Animals↗

PubMed1984

[Acquisition of a lever press behavior by mice in a water reinforcement situation].

An operant chamber for mice, consisting of two adjacent compartments of W 130 X L 120 X H 150 mm, with a liquid dispenser which is operated by lever press was prepared. Using the apparatus, the applicability of mice for the study of learning of lever press behavior in a water reinforcement situation was investigated. Animals were deprived of water in the home cage and water was only supplied in the operant chamber by the lever press. A session of 15 min training was performed daily. By continuous reinforcement schedule, animals learned the lever pressing by 3 sessions. With these trained animals which attained more than 150 responses further experiments with a fixed ratio (FR) schedule was made, from FR 1 to FR 20. The best increase in responses was observed when the FR was regularly and gradually stepped up from 1 to 20 by every 5 sessions. Scopolamine, 1 mg/kg ip, significantly suppressed the lever press at FR 1 sessions, and the latency time until the first lever press was also prolonged significantly in these sessions. Thus, the applicability of mice for the study of learning of lever press behavior and the experimental schedules were established.

Animals↗

PubMed1986

Response repetition in pigeons: pharmacological and behavioral specificity.

Using a reinforcement schedule that arranges random sequences of reinforcements over two response keys, low and high probabilities of repetition of non-reinforced responses were generated in two groups of pigeons (n = 3 per group) by varying the probability of reinforcement for responding on the key to which reinforcement was assigned. Unlike rats, the pigeons did not show a tendency to repeat just-reinforced responses, but showed a strong position bias, that was reduced by additional feeding and extinction, but not by any of the drug treatments. Apomorphine increased response repetition, irrespective of the control probability of repetition; d-amphetamine increased low probabilities of repetition, but decreased high probabilities. Chlordiazepoxide and scopolamine selectively decreased high probabilities of repetition; phencyclidine and pentobarbital selectively increased low probabilities of repetition. Morphine, haloperidol, chlorpromazine, additional feeding, and extinction did not affect repetition of non-reinforced responses. Extinction increased perseveration, whereas drug effects on perseveration were not observed. Drug-induced changes of patterning of responses as exemplified herein by drug-induced alterations of repetitiveness may be relevant to the interpretation of drug effects upon performance brought about by other behavioral processes such as discrimination.

Animals↗

PubMed1998

Effect of reinforcement on facial responsivity and persistence in children with attention-deficit hyperactivity disorder.

Children with Attention Deficit-Hyperactivity Disorder (ADHD) may learn poorly under conditions of inconsistent (partial) reinforcement because they are easily frustrated and fail to develop persistence. To test this hypothesis, a nonsense word spelling task was used with 22 ADHD and 20 control children to investigate the effects of partial and continuous reinforcement on facial responsivity (frustration measure), words spelled correctly (learning performance measure), and persistence ratings. Partially reinforced ADHD children manifested higher levels of frustration in both acquisition and extinction than any other group and gave significantly lower persistence ratings across acquisition than partially reinforced control children. ADHD children spelled fewer words correctly than controls, regardless of reinforcement schedule. These findings suggest that partial reinforcement training develops persistence in normal but not ADHD children. The findings have theoretical implications for the etiology of ADHD as well as practical implications for designing behavior modification programs to treat ADHD.

Attention↗

PubMed1975

Stimulus change as a factor in response maintenance with free food available.

Rats bar pressed for food on a reinforcement schedule in which every response was reinforced, even though a dish of pellets was present. Initially, auditory and visual stimuli accompanied response-produced food presentation. With stimulus feedback as an added consequence of bar pressing, responding was maintained in the presence of free food; without stimulus feedback, responding decreased to a low level. Auditory feedback maintained slightly more responding than did visual feedback, and both together maintained more responding than did either separately. Almost no responding occurred when the only consequence of bar pressing was stimulus feedback. The data indicated conditioned and sensory reinforcement effects of response-produced stimulus feedback.

Acoustic Stimulation↗

PubMed1984

Isobias and alloiobias functions in animal psycophysics.

An analogue of the human yes-no detection task was used to train six pigeons to discriminate luminance differences under two different reinforcer-scheduling procedures. When a controlled reinforce-ratio procedure was used, relative stimulus frequency was constant at .5, and relative reinforcer frequency for correct detections was held constant at three different values for each of five luminance differences. When an uncontrolled reinforcer-ratio procedure (the typical detection paradigm) was used, relative reinforcer frequency for correct detections was allowed to covary with changes in relative stimulus frequency for each of five luminance differences. Two measures of bias, response bias (Davison & Tustin, 1978) and the detection-theory likelihood-ratio measure (beta obt), were compared. The controlled reinforcer-ratio procedure generated equal- or iso-response-bias functions, and the uncontrolled reinforcer-ratio procedure gave changing or alloio-response-bias functions. The Davison-Tustin model accounted for 88% and 93% of the data variance in the controlled and uncontrolled reinforcer-ratio procedures, respectively. The best-fitting equal-beta functions accounted for an average of 53% and 69%, respectively, in the two procedures. In addition, neither procedure gave constant measures of beta obt for constant bias manipulations across different discriminability measures.

Animals↗

PubMed1965

SEQUENTIAL RESPONSE EFFECTS IN THE WHITE RAT DURING CONDITIONING AND EXTINCTION ON A DRL SCHEDULE.

Sequential IRT data were obtained for three rats on a DRL 60-sec reinforcement schedule. It was found that first-order sequential dependencies exist under this schedule, including the partial dependence of the length of any given IRT on the length of the preceding IRT. The sequential analysis also served to extend the finding in the literature, based on frequency distributions, that the likelihood of a reinforced IRT is greater after a reinforced IRT than a non-reinforced IRT. Rapid extinction and reconditioning were obtained.

Extinction, Psychological↗

PubMed1978

The effects of scopolamine on extinction and spontaneous recovery.

The effects of scopolamine hydrobromide on baseline extinction levels and spontaneous recovery were assessed. Rats were trained on one of four reinforcement schedules (CRF, FR 10, FR 20, FR 40) with either food or water reinforcement. Scopolamine increased response rates in extinction and spontaneous recovery following training on all four schedules when the reinforcer was water, but had no effect on responding previously maintained by food. The results are discussed in terms of the limitations of a general theory of a cholinergic system mediating all suppressed behavior and the effects of anticholinergic drugs on central thirst mechanisms and consummatory behavior.

Animals↗

PubMed2002

The effect of excitotoxic lesions of the pedunculopontine tegmental nucleus on performance of a progressive ratio schedule of reinforcement.

The pedunculopontine tegmental nucleus has connections with sites in both dorsal and ventral striatum, and a number of studies have suggested that it has a role in reward-related behaviour. The present experiment aimed to investigate the perception of reward in pedunculopontine tegmental nucleus-lesioned rats responding for food under a progressive ratio schedule, which measures willingness to work for a given reward. Rats were trained on a progressive ratio-5 schedule for food reward, then given ibotenic acid or sham lesions of the pedunculopontine tegmental nucleus. Their performance under this schedule was examined again following recovery from surgery. Compared with sham-lesioned rats, those with lesions of the pedunculopontine tegmental nucleus showed significantly reduced breaking points and significantly longer post-reinforcement pauses. However, there was no difference between the groups in their latency to collect food pellets once earned, suggesting that pedunculopontine tegmental nucleus excitotoxin and sham-lesioned rats were equally motivated by the presence of food. Excitotoxin-lesioned rats made significantly more responses on the control lever and more entries to the food hopper as progressive ratio increment increased, but did not differ from controls when the schedule requirement was low. These results are interpreted as indicating no global loss of motivation, since lesioned rats performed normally at low schedule requirements, and were as fast as controls to collect pellets. But as the schedule requirement increased, excitotoxin-lesioned rats showed reductions in responding on the active lever (that is, a reduction in breaking point) and an increase in inappropriate responses towards the food hopper and the control lever.We consider these data to indicate that the behavioural deficits in pedunculopontine-lesioned rats arise not from a sensory or hedonic change, but from alteration in the control of motor output.

Animals↗

PubMed1976

Signalled reinforcement and multiple schedules.

The responses of four pigeons were first reinforced in the presence of two different wave-lengths (green and red) on a two-ply multiple schedule with identical variable-interval 3-min schedules of reinforcement associated with each component. While the constant-component reinforcement schedule remained unchanged during the experiment, the schedule associated with the variable component was changed to (1) signalled variable time, (2) unsignalled variable time, or (3) signalled variable interval. The probability with which the availability of the reinforcer was signalled in the variable-interval schedules was either 0.5 or 1.0. Positive contrast occurred in both signalled variable-interval and variable-time schedules, but only when the availability of all the variable-component reinforcers was signalled. Signalling the availability of only 50% of the reinforcers in signalled variable-interval schedules resulted in negative induction. The present data suggest that positive behavioral contrast resulting from signalled reinforcer availability is due to the presence of an extinction-correlated stimulus.

Journal Article↗

PubMed1986

Superimposition of response-independent reinforcement.

Studies that have superimposed response-independent reinforcement (or reinforcers scheduled by contingencies placed on the absence of responding) upon conventional response-dependent schedules are reviewed. In general, providing alternative sources of reinforcement reduced response rates below the levels observed when alternative reinforcement was absent. However, response-rate elevation was sometimes found, particularly when rates of superimposed response-independent reinforcement were low. Superimposition of schedules providing reinforcers contingent on the absence of responding usually produced more severe response-rate decrements than superimposition of response-independent reinforcement. A variant of Herrnstein's equation, which assumes that some of the alternative reinforcers function as if they were delivered by baseline response-dependent source of reinforcement, is in qualitative agreement with the overall body of results obtained, and can predict both increases and decreases in response rate as resulting from superimposed reinforcers.

Journal Article↗

PubMed1964

AN AVERSIVE STIMULUS AS A CORRELATED BLOCK COUNTER IN FR PERFORMANCE.

After the performances of two pigeons had stabilized on an FR 100 grain reinforcement schedule, response-contingent shock was introduced in the form of a block counter. When shock intensity increased in successive thirds of the ratio, duration of post-reinforcement pauses increased and local rate in an advanced part of the ratio declined. With decrements of shock intensity in successive thirds of the ratio, running rate was not consistently affected but pauses after reinforcements were longer than those under the increasing counter. The results are interpreted in terms of the interaction among some controlling variables operating in the behavioral chain.

Animals↗

PubMed1990

Absence of anticipatory contrast in rats trained on multiple schedules.

Rats were trained on three- and four-component multiple schedules in which two of the components were correlated with identical reinforcement schedules that remained unchanged throughout training. These target components differed in terms of whether their respective following schedules were either higher or lower in value. Unlike corresponding experiments previously reported with pigeons, higher response rates occurred in the target component followed by a higher valued schedule than in the target component followed by the lower valued schedule. Overall contrast effects occurred independently of these sequential effects, but were inconsistent across subjects. The results suggest that the effects of a following schedule of reinforcement are opposite for pigeons and rats, and that one reason previous studies have often failed to show contrast effects with rats is that the effects of the following schedule in rats are in competition with contrast dynamics.

Animals↗

PubMed1975

Ethanol as a reinforcer for rats: effects of concurrent access to water and alternate positions of water and ethanol.

Water and ethanol solutions were concurrently made available on a continuous reinforcement schedule to 4 food-deprived male albino rats during daily 1-hr sessions in an operant conditioning chamber equipped with 2 levers and 2 liquid dippers. The number of ethanol reinforcements substantially exceeded the number of water reinforcements for each rat at each concentration studied (8, 16, and 32% w/v). Water reinforcements were low in number and did not vary with ethanol concentration. As the ethanol concentration was increased, the number of ethanol reinforcements obtained decreased, while the quantity consumed (mg/100 g of body weight/hr) increased. The highest rate of responding occurred at the beginning of the session.

Alcohol Drinking↗

PubMed2000

Clozapine does not induce a motor impairment in operant responding for heat reinforcement.

This experiment examined the effects of intraperitoneal (i.p.) clozapine (CLZ) compared to haloperidol (HAL) on operant responding for heat reinforcement in a cold environment (-8 degrees C). Three doses of CLZ (1, 3 and 5 mg/kg) were found to dose-dependently increase responding for heat while lowering core temperature (T(c)) only at the highest dose. Three doses of HAL (0.1, 0.3 and 0.5 mg/kg) dose-dependently decreased operant responding which resulted in a dose-dependent decrease in T(c). The highest dose of CLZ was then tested in two other paradigms: a reinforcement schedule in which heat was available as long as the lever was held down, and a temperature gradient (range 7-45 degrees C) in which access to heat required minimal motor effort. The ad libitum reinforcement schedule still did not provide enough heat to overcome the hypothermic effects of CLZ. However, in the gradient, rats receiving CLZ selected a warmer region of the gradient, and T(c) was higher than that of controls. These data support CLZ's reputation for having minimal motor side effects. Unlike HAL, the hypothermic effects of CLZ appear to be unrelated to effects of the drug on movement.

Analysis of Variance↗

PubMed1990

Bromocriptine self-administration and bromocriptine-reinstatement of cocaine-trained and heroin-trained lever pressing in rats.

Rats were trained to lever press for intravenous cocaine (1.0 mg/kg/injection) and then switched to bromocriptine (0.3, 1.0, or 3.0 mg/kg/injection) on a FR-1 reinforcement schedule. Bromocriptine sustained responding at all three doses; hourly drug intake increased linearly with log-dose. In a second experiment, animals were trained to respond for cocaine (1.0 mg/kg/injection) or heroin (0.1 mg/kg/injection) reinforcement; drug was available for the first 2 h of each daily session; saline was substituted for cocaine or heroin for 5 subsequent hours. One hour into each saline substitution session, an intravenous injection of saline or bromocriptine (0.0, 0.5, 1.0, or 2.0 mg/kg) was given. Bromocriptine reinstated both cocaine-trained and heroin-trained lever pressing; under these conditions, the drug was most effective in the heroin-trained animals. Reinforcing doses of clonidine (0.0625 and 0.125 mg/kg), methohexital, and nicotine (0.05 and 0.1 mg/kg), and a sub-intoxicating dose of ethanol (2 g/kg) failed to reinstate cocaine-trained responding. These data indicate that bromocriptine has cocaine-like and heroin-like stimulus and reinforcing effects.

Animals↗