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At least 649 records · Page 36Linked to original sources
PubMed2000

Rats selectively bred for responsiveness to 5-hydroxytryptamine(1A) receptor stimulation: differences in differential reinforcement of low rate 72-second performance and response to serotonergic drugs.

High (+/-)-8-hydroxy-dipropylaminotetralin HBr (8-OH-DPAT)-sensitive (HDS) rats and low 8-OH-DPAT-sensitive (LDS) rats were selectively bred for differences in sensitivity to the hypothermic effect of the 5-hydroxytryptamine(1A) (5-HT(1A)) receptor agonist 8-OH-DPAT in 30 to 35-day-old rat pups. These rats were trained on the differential reinforcement of low rate 72-s operant schedule. On this schedule, LDS rats had a higher response rate and a lower reinforcement rate than HDS rats. Drugs with primary action on the 5-HT system, 8-OH-DPAT, ketanserin, and fluoxetine, decreased response rate of HDS and LDS rats but increased the reinforcement rate of only the LDS rats. However, a drug with primary action on the norepinephrine system, desipramine, decreased response rate and increased reinforcement rate of HDS and LDS rats, suggesting that norepinephrine function was similar in the two lines of rats. The finding with desipramine indicates that increases in reinforcers on the differential reinforcement of low rate 72-s task are not simply dependent on baseline response or reinforcement rate. We also observed that 8-OH-DPAT engenders a greater hypothermic response in adult (90-day-old) HDS rats than in adult LDS rats. The 5-HT(1A) receptor antagonist WAY-100635 antagonized the hypothermic response. Tissue levels of 8-OH-DPAT from several brain regions in LDS and HDS rats did not differ from each other at either 15- or 30-min postinjection. Because the LDS and HDS rats have different responses to 5-HT-acting drugs, these rats may be useful for studying the role of the serotonergic system in depression.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2003

Importance of trials versus accumulating time across trials in partially reinforced appetitive conditioning.

Four experiments with rats examined partial reinforcement in appetitive conditioning. In Experiment 1, adding nonreinforced trials to a continuous reinforcement schedule slowed acquisition, whereas deleting reinforcers did not. Trial massing suppressed performance and learning. In Experiment 2, conditioning with a short conditioned stimulus (CS) was rapid, and partial reinforcement with a short CS was as effective as continuous reinforcement with equal accumulated time in the CS. In Experiment 3, conditioning was nevertheless influenced by the probability of reinforcement. In Experiments 3 and 4, conditioning was especially disrupted when nonreinforced trials preceded reinforced trials closely in time. The results underscore the importance of temporal variables in conditioning but are more consistent with trial-based accounts than time-accumulation accounts of conditioning.

Animals↗
PubMed1991

Common mechanisms of reinforcement from alcohol and other drugs.

Vulnerability to substance abuse is an important social and scientific issue. A critical aspect of this phenomenon is the degree to which individuals who abuse one substance are likely to abuse other substances. The extent to which several pharmacologically distinct drugs will come to serve as positive reinforcers within genetically defined subjects defines their community with respect to abuse liability. Questions in this area are directed at determining whether reinforcement from and abuse of alcohol and other drugs define variations within a single behavioral phenomenon, or whether reinforcement and abuse must be individually defined for each substance involved. Previous studies have shown that ethanol can be readily established as a positive reinforcer in LEWIS rats and C57BL/6J mice. In low ethanol preferring F344 rats, ethanol maintains significant but low levels of responding. Ethanol does not maintain behavior in BALB/cJ or DBA/2J mice. These genotypic patterns of reinforcement from ethanol appear to correlate highly with patterns of reinforcement from cocaine and opiates. Other studies suggest that some aspects of drug self-administration may be mediated in part by common dopaminergic and serotonergic mechanisms, and animals which differ in ethanol drinking behavior show substantial differences in parameters of serotonergic function. Thus, there may exist important genetic determinants of drug reinforced behavior.

Alcohol Drinking↗
PubMed1990

Learning and memory is reflected in the responses of reinforcement-related neurons in the primate basal forebrain.

Certain basal forebrain neurons encode the learned reinforcement value of objects: they respond differentially to visual stimuli that signal availability of fruit juice (positively reinforcing) or saline (negatively reinforcing) obtained by lick responses in visual discrimination tasks. In this report we describe the rapid, learning-related changes in the responses of these neurons during the acquisition and reversal of the reinforcement contingency of a visual discrimination reversal task. The same neurons also responded differentially to novel and familiar stimuli in 2 recognition memory tasks, in which monkeys applied the learned rule that lick responses to novel stimuli elicited saline and responses to familiar stimuli elicited juice. These differential responses to novel and familiar stimuli thus reflected the reinforcement value of the stimuli. A single presentation of a novel or a familiar stimulus was sufficient to elicit a differential response which was maintained even when the stimulus had not been seen recently. The maintenance of the differential response indicates that these neurons are influenced by a durable memory for the stimuli, estimated to be 30 trials on average. These differential neurons were recorded in the substantia innominata, the diagonal band of Broca, and a periventricular region of the basal forebrain. The responses of the reinforcement-related neurons in these 3 regions were similar in most respects. These results support the conclusion that basal forebrain neurons respond to sensory stimuli that, through learning of different contingencies, signal the availability of reinforcement. We suggest that the properties of learning and memory reflected in these neuronal responses are due to afferent pathways from ventromedial regions of the prefrontal and temporal cortices and the amygdala, and that the responses of these neurons provide an enabling mechanism that facilitates the operation of diverse cortical regions in which specific sensory, motor, or mnemonic functions take place.

Animals↗
PubMed1987

Amygdalectomy and disconnection in visual learning for auditory secondary reinforcement by monkeys.

Nine monkeys in 3 groups took part in an experiment on visual discrimination learning set in an automatic apparatus. Each new visual discrimination problem was solved using auditory secondary reinforcers. Primary food reinforcement was delivered only after a new problem had been solved to a criterion, and the problem was then replaced by a new one; thus, within-problem learning relied purely on secondary and not on primary reinforcement, but the secondary reinforcers were associated with primary reinforcement. Bilateral amygdalectomy severely retarded within-problem learning. Disconnection of the amygdala from auditory input, by crossed unilateral lesions of amygdala and of auditory cortex combined with forebrain commissurotomy, had a similar effect to that of bilateral amygdalectomy. Disconnection of the amygdala from visual association cortex left learning unimpaired. Thus, for normal performance in this task, interaction of the amygdala with the sensory modality of the secondary reinforcer was essential, but interaction of the amygdala with the sensory modality of the discriminative stimuli was not necessary. It was concluded that the amygdala is involved in associating stimuli with the primary reinforcing attributes of food reward, and not with its other attributes.

Amygdala↗
PubMed1984

Reinforcing and discriminative stimulus properties of mixed agonist-antagonist opioids.

Nine mixed agonist-antagonist opioids were evaluated in macaque monkeys for their ability to serve as positive reinforcers and for their discriminative stimulus similarity to etorphine and ethylketazocine. For tests of reinforcing properties, various doses of each drug were substituted for codeine under a fixed-ratio 30 time-out 600 sec schedule of i.v. delivery. Discriminative properties were assessed in separate groups of monkeys for which etorphine and saline, or ethylketazocine and saline, were established as discriminative stimuli for responses maintained under a fixed-ratio 20 schedule of food delivery. Two patterns of reinforcing and discriminative stimulus properties were observed. Buprenorphine, butorphanol, GPA 1657, nalbuphine, propiram and WY 16225 (dezocine) functioned as positive reinforcers and occasioned etorphine-appropriate but not ethylketazocine-appropriate responses. dl-Profadol also functioned as a positive reinforcer; its stereoisomers occasioned etorphine-appropriate but not, in general, ethylketazocine-appropriate responses. In contrast, levallorphan and oxilorphan did not function as positive reinforcers and occasioned ethylketazocine-appropriate but no more than 30% etorphine-appropriate responses. Under these experimental conditions, the reinforcing and discriminative stimulus profiles of the mixed agonist-antagonist opioids paralleled those of etorphine-like (mu) or ethylketazocine-like (kappa) opioid agonists.

Animals↗
PubMed1983

Differential-reinforcement-of-low-rate 72-second schedule: selective effects of antidepressant drugs.

The effects of antidepressant drugs in rats responding under a differential-reinforcement-of-low-rate 72-sec schedule were assessed. Seven clinically used tricyclic antidepressant drugs (imipramine, desipramine, chlorimipramine, protriptyline, nortriptyline, amitriptyline and doxepin), two atypical antidepressants (iprindole and mianserin) and a monoamine oxidase inhibitor (tranylcypromine) dose-dependently reduced response rate and increased reinforcement rate. Nomifensine, an atypical antidepressant which has been reported to have psychomotor stimulant properties and abuse potential, increased response rate and decreased reinforcement rate. Chlorpromazine, an antipsychotic agent, and diphenhydramine, an antihistamine, have been reported to produce effects similar to antidepressants in several behavioral tests, but neither of these drugs mimicked the actions of antidepressants on responding under a differential-reinforcement-of-low-rate 72-sec schedule. Chlorpromazine decreased response rate but did not increase reinforcement rate. Diphenhydramine did not have consistent effects but tended to decrease reinforcement rate. These findings suggest that behavior maintained by the differential-reinforcement-of-low-rate schedule may be selectively affected by antidepressants that have no psychomotor stimulant properties.

Animals↗
PubMed1981

Responses eliminated by noncontingent or negatively contingent reinforcement recover in extinction.

Autoshaped key pecking in pigeons was eliminated by presenting reinforcers only during non-CS periods (negatively contingent reinforcement) or in both non-CS and CS periods (noncontingent reinforcement). In either case, when all reinforcers were subsequently removed (simple extinction), responding recovered strongly (Experiment 1). Recovery in extinction occurred only if the CS was in a conditioned state when non-CS reinforcers were introduced (Experiment 2). Recovery from noncontingent reinforcement was virtually complete, since total responding in extinction after response elimination was not less than in control groups extinguished without an intervening response-elimination phase (Experiment 3). Recovery also occurred for nonautoshapable, instrumentally reinforced key pecking (Experiment 4). The hypothesis that recovery is due to reinstatement of the non-CS stimulus conditions of acquisition (absence of food) was not supported (Experiments 5 and 6). Other accounts of recovery are considered.

Animals↗
PubMed1980

Comparison of two reinforcement strategies in vocational-skill training of mentally retarded persons.

While recommendations concerning reinforcement strategies in vocational training of retarded persons range from the use of minimal social reinforcement to the use of extra social and edible reinforcement, empirical comparisons of such strategies could not be found in the literature. Four experiments were conducted to compare minimal social reinforcement to social plus edible reinforcement while lower functioning retarded clients were taught assembly tasks of varying complexities. In all experiments, the extra reinforcement generally facilitated the learning of a task to criterion in terms of training time, number of trials, total number of errors, and the proportion of errors on learned steps. Moreover, a preference test showed that the majority of clients preferred the extra reinforcement condition.

Adolescent↗
PubMedDate not supplied

The effect of two forms of learning reinforcement upon parental retention of CPR skills.

PURPOSE: To evaluate the effect of two forms of reinforcement upon the retention of CPR psychomotor skills in parents of high-risk infants. METHOD: A pretest/posttest, 3-group design was done with a sample of 69 parent volunteers. Reinforcement with hands on practice was given to one group; a second group had reinforcement by observing a videotape, and the third group had no reinforcement strategy. CPR skills were measured by a checklist. FINDINGS: Paired t-test showed significant differences in pretest and posttest scores for all three groups. Several CPR skills were missed on the final test more frequently than others. One-way ANOVA also showed a significant difference when comparing the control group with the hands-on reinforcement group. CONCLUSIONS: Reinforcement of CPR skills should be an ongoing process. The groups who had reinforcement with hands-on practice retained the most skills.

Adolescent↗
PubMed1997

The relationship between reinforcing effects and in vitro effects of D1 agonists in monkeys.

The reinforcing effects of many psychomotor stimulants have been related to increased dopaminergic neurotransmission and stimulation of central nervous system (CNS) dopamine (DA) receptors. Consistent with this notion, some drugs that directly stimulate DA receptors have been found to function as positive reinforcers. The present experiments were designed to examine why some, but not all, D1 receptor agonists can function as reinforcers in rhesus monkeys by comparing behavioral and CNS in vitro measures of potency and efficacy. Seven rhesus monkeys were allowed to self-administer cocaine under a progressive-ratio (PR) schedule until stable responding was established. Various doses of D1 agonists, previously reported to function as positive reinforcers, were then made available for self-administration. Stimulation of cAMP production in rhesus and rat striatal tissue was studied for these compounds and for D1 agonists previously reported not to function as positive reinforcers in monkeys (SKF 38393, SKF 77434 and S(-)-6-BrAPB). Blockade of DA uptake in rat striata was also examined for all compounds. SKF 81297, SKF 82958 and R(+)-6-BrAPB maintained responding under the PR schedule and did not differ significantly in efficacy as positive reinforcers; SKF 81297 was less potent than the other two agonists. SKF 81297, SKF 82958 and R(+)-6-BrAPB stimulated higher levels of cAMP production in rhesus striata than did SKF 38393, SKF 77434 and S(-)-6-BrAPB. In contrast, all compounds blocked DA uptake. Thus, reinforcing efficacy among D1 agonists increases with efficacy in stimulating D1 receptors.

Animals↗
PubMed1998

Altered reinforcement mechanisms in attention-deficit/hyperactivity disorder.

The present study tested eight boys with attention-deficit/hyperactivity disorder (ADHD) and 12 normal boys (comparison group), aged 7-12 years, to investigate the hypothesis that ADHD is associated with a steeper and shorter delay-of-reinforcement gradient than is normal. A two-component schedule of reinforcement was used to deliver trinkets or coins as reinforcers in a game-like test. One component was marked by a signal. During this period reinforcers (coins or trinkets) were delivered every 30 s. This component is called a 30-s fixed interval (FI) schedule of reinforcement and measures changes in reactivity to reinforcers. The other component was in effect when the signal was turned off. Then no reinforcer was ever delivered. This is called an extinction (EXT) component and measures primarily sustained attention. The ADHD children gradually developed hyperactivity to a large extent consisting of bursts of responses with short interresponse times (IRTs) during both schedule components. The response bursts not only constituted a substantial portion of the ADHD overactivity, but may well be a key component of the behaviour commonly described as impulsiveness, the key behavioural characteristic of ADHD. In addition, the ADHD children showed behaviour during the extinction component that may well be described as a sustained-attention deficit: initially stopping when the signal was turned off and then resuming responding some time thereafter as if the signal had been turned on again. The comparison group ceased responding during extinction and did not show impulsiveness. The findings were in accordance with a steeper and shorter delay gradient in ADHD.

Attention↗
PubMed1996

Alcohol reinforcement and neuropharmacological therapeutics.

The pleasant subjective effects produced by alcohol undoubtedly reinforce drinking behaviour. Alcohol positively reinforces or rewards drinking by producing a mild euphoria. Alcohol also has anxiolytic effects that negatively reinforce drinking. The reinforcing effects of alcohol are mediated by several neurochemical systems, with dopamine and serotonin playing major roles in reward and the gamma-aminobutyric acid-benzodiazepine receptor system playing a major role in negative reinforcement. Research from our laboratory suggests that the behavioural effects of alcohol change when blood alcohol levels are changing and that these changes correspond to alterations of specific neurochemical systems. Behavioural activation and reward effects appear to occur as blood alcohol concentrations (BACs) increase. Depressive and aversive effects of alcohol occur during the period when BACs decrease. The observed correlation between behavioural and neuropharmacological changes and alcohol consumption suggest that alcohol produces a unique cascade over time that may provide clues to its long-sought specific mechanisms of action. In alcohol-dependent individuals, chronic exposure to alcohol may alter the function and communication between the liver, brain and other vital organ systems involved in hunger and the maintenance of nutrition. Under such conditions, the importance of alcohol in the diet may be enhanced such that hunger signals in the alcohol-dependent individual motivate the consumption of alcohol. Therefore, hunger for alcohol may provide an additional source of reinforcement. Endogenous opioid mechanisms may be important in this form of alcohol reinforcement.

Alcohol Drinking↗
PubMed1963

Effects of increment size and reinforcer volume on progressive ratio performance.

The progressive ratio schedule requires the subject to emit an increasing number of responses for each successive reinforcement. Eventually, the response requirement becomes so large that the subject fails to respond for a period of 15 min and thereby terminates the session. This point is arbitrarily defined as the "breaking point" of the subject's performance. The measure is quantified in terms of the number of responses in the final completed (i.e., reinforced) ratio run of the session. Previous work has shown that this measure varies as a function of several motivational variables and may thus be useful as an index of reinforcement strength. The present study is an extension of that work. The subjects were four rats. In the first experiment, the effects of the size of the increment by which each ratio run increased were studied. In two additional experiments, the volume of a liquid reinforcer was varied using both large and small ratio increments. The results indicate that the number of responses in the final completed ratio run increases as a function of the size of the ratio increment. However, the number of reinforcements obtained by the animals per session declines sharply. When large ratio increments are used, the number of responses in the final ratio increases as a function of the volume of the reinforcer, but when small increments are used, progressive satiation results in a decline in performance with the larger volumes of liquid.

Animals↗
PubMed1997

Comparison of the tissue response to absorbable self-reinforced polylactide screws and metallic screws in the fixation of cancellous bone osteotomies: an experimental study on the rabbit distal femur.

The availability of absorbable fracture-fixation devices for clinical use calls for better knowledge of the reaction of bone tissue to absorbable polyester implants as compared with similar metallic devices. To examine and compare the tissue response to biodegradable and metallic screws within cancellous bone, a transverse transcondylar osteotomy of the distal femur was fixed with absorbable self-reinforced polylevolactide screws in 35 rabbits and with stainless-steel screws in 35 rabbits. New bone formation and consolidation of the osteotomy were examined histologically, histomorphometrically, and microradiographically within standardized sample fields 1, 3, 6, 12, 24, 36, and 48 weeks postoperatively. The intact contralateral femur served as the control. A vigorous osteoconductive response to the polylevolactide screws was observed at 3 weeks postoperatively, and the osteoid surface fraction was significantly higher in all follow-ups than in the contralateral femora. In the femora with metallic screws, new bone formation was seen 3, 6, and 12 weeks postoperatively, but at 24, 36, and 48 weeks the osteoid surface fraction did not differ significantly from that of the intact control femora. The total bone area was significantly larger in the femora with self-reinforced polylevolactide screws than in the control bone 6-48 weeks postoperatively; in the femora with metallic screws, this was found only at 6 and 12 weeks. After 48 weeks, the femora fixed with metallic screws had statistically smaller total bone area than the intact control femora. Solid bone union was seen in 84% of the osteotomies in the self-reinforced polylevolactide group and in 76% of those in the metallic group after 3 weeks or more. No signs of degradation of the self-reinforced polyleuolactide implant and only a mild foreign-body reaction with no accumulations of inflammatory cells to either self-reinforced polylevolactide or metallic screws were observed during the follow-up period. Both types of screws seemed to induce an osteostimulatory response around their threads. This phenomenon was transient for metallic screws but lasted for at least 48 weeks for self-reinforced polylevolactide screws. The polylevolactide screw does not seem to cause osteopenia at the implantation site. The fixation properties of both self-reinforced polylevolactide screws and metallic screws appear to be sufficient for the fixation of small fragments of cancellous bone.

Animals↗
PubMed1994

Glutamate-dopamine interactions in the ventral striatum: role in locomotor activity and responding with conditioned reinforcement.

Previous evidence suggests that glutamatergic limbic afferents participate in the potentiation of responding with conditioned reinforcement produced by intra-accumbens d-amphetamine. The present experiments were designed to investigate glutamate-dopamine interactions in the ventral striatum in both conditioned reinforcement and locomotor activity. Glutamate receptor agonists and antagonists were infused into the nucleus accumbens both alone and in combination with 3 micrograms d-amphetamine, and the effects of these interactions on responding with conditioned reinforcement and locomotor activity were measured. The glutamate receptor agonists NMDA, AMPA and quisqualate (agonists at the NMDA, AMPA and metabotropic glutamate receptor subtypes, respectively) and the antagonists AP5 and CNQX, (antagonists at the NMDA and AMPA receptor subtypes, respectively) were used in these investigations. These compounds were used in a dose range of 0.3 to 3 nmol, except CNQX, which was used in 0.2 to 2 nmol doses. While all agonists and antagonists increased locomotor activity when administered alone, the antagonists attenuated the locomotor response to d-amphetamine. In contrast, the agonists AMPA and quisqualate enhanced d-amphetamine-induced locomotor activity, although NMDA interfered with the effects of d-amphetamine. In the conditioned reinforcement paradigm, both the agonists and the antagonists abolished amphetamine's potentiation of responding with conditioned reinforcement, suggesting that the glutamatergic transmission of information about the conditioned reinforcer could be blocked by glutamate receptor antagonists and disrupted by administration of the agonists. The dissociation between the effects of these excitatory amino acids on amphetamine-induced locomotor activity versus their effects on amphetamine's potentiation of responding with conditioned reinforcement provides insight into the nature of the reward enhancement by accumbens dopamine versus its locomotor stimulant effects.

Animals↗
PubMed2003

Measuring impulsivity in mice using a novel operant delayed reinforcement task: effects of behavioural manipulations and d-amphetamine.

RATIONALE: The increasing use of genetically modified mice to probe genetic contributions to normal and abnormal behaviours requires the development of sensitive and selective behavioural tasks. OBJECTIVES: To develop a discrete trial assay of impulsivity (delayed reinforcement) that is tractable in mice utilising a mouse operant nine-hole box apparatus and to specify the task with respect to behavioural and pharmacological manipulations. METHODS: Mice were trained to respond with a nose-poke to one of two visual stimuli; one response resulted in a small quantity of reinforcer, the other in a larger quantity of reinforcer. As the session proceeded increasing delay was introduced onto the response leading to the large reward. Hence, the nature of the choice was a small quantity of reinforcer immediately versus a larger but progressively delayed amount of reinforcer. At stable baseline performance the mice were challenged with a variety of task manipulations and systemic d-amphetamine in order to discern aspects of the underlying psychological and neurochemical substrates of the choice behaviour. RESULTS: The mice showed a systematic shift in responding away from the large reinforcer with increasing delay (0, 2, 4, 8, 12 s), such that at the longest delay >80% of nose-pokes were for the smaller, immediate reinforcer. Task manipulations indicated that behaviour was controlled in a trial discrete manner by the contingency between delay and reward and was not due to non-specific factors such as satiation. d-Amphetamine had complex, dose dependent effects on choice behaviour which revealed dissociations between impulsive choice and hyperactivity. CONCLUSIONS: We have successfully developed an assay of impulsivity in mice that will be of utility to examine impulsive behaviours and their genetic substrates. In addition, our data provided evidence of distinct dopaminergic mechanisms mediating aspects of impulsivity and hyperactivity.

Amphetamine↗
PubMed1987

Strength and strength retention in vitro, of absorbable, self-reinforced polyglycolide (PGA) rods for fracture fixation.

The initial shear strength and changes in flexural strength of self-reinforced, absorbable polyglycolide (PGA) composite rods, submerged in distilled water (at 37 degrees C) for a period of 6 wk, were investigated. The recently developed self-reinforced absorbable material consists of an absorbable polymeric matrix reinforced with fibres of the same polymer. The initial shear strength of self-reinforced cylindrical PGA rods with a diameter of 3.2 mm was 250 MPa and the initial flexural strength of the rods was 370 MPa. During the first week of immersion the level of flexural strength decreased very little i.e. to 320 MPa. The loss of flexural strength increased after 1 wk immersion. However, after 3 wk it was 90 MPa. After 5 wk the flexural strength decreased to the level of strength of cancellous bone i.e. 10-20 MPa. The gamma-irradiation of the PGA rods (total dosage 2.5 Mrad) decreased the initial bending strength to 300 MPa but the hydrolytic behaviour of the rods was not changed. The in vitro strength and the strength retention of self-reinforced PGA rods are clearly better than the corresponding values for self-reinforced glycolide/lactide copolymer rods which we developed recently. Self-reinforced PGA rods are now used routinely in Helsinki University Central Hospital in the treatment of certain types of cancellous bone fracture.

Benzenesulfonates↗