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1.
The acute behavioral effects of atropine sulfate were assessed using a battery of complex food-reinforced operant tasks that included: temporal response differentiation (TRD, n = 7); delayed matching-to-sample (DMTS, n = 6), progressive ratio (PR, n = 8), incremental repeated acquisition (IRA, n = 8), and conditioned position responding (CPR, n = 8). Performance in these tasks is thought to depend primarily upon specific brain functions such as time perception, short-term memory and attention, motivation, learning, and color and position discrimination, respectively. Atropine sulfate (0.01-0.56 mg/kg iv), given 15-min pretesting, produced significant dose-dependent decreases in the number of reinforcers obtained in all tasks. Response rates decreased significantly at greater than or equal to 0.03 mg/kg for the learning and discrimination tasks, at greater than or equal to 0.10 mg/kg for the motivation and short-term memory and attention tasks, and at greater than or equal to 0.30 mg/kg for the time perception task. Response accuracies were significantly decreased at doses greater than or equal to 0.10 mg/kg for the learning, discrimination, and short-term memory and attention tasks, and at greater than or equal to 0.30 mg/kg for the time perception task. Thus, the order of task sensitivity to any disruption by atropine is learning = color and position discrimination greater than time perception = short-term memory and attention = motivation (IRA = CPR greater than TRD = DMTS = PR). Thus in monkeys, the rates of responding in operant tasks designed to model learning and color and position discrimination were the most sensitive measures to atropine's behavioral effects. Accuracy in these same task was also disrupted but at higher doses. These data support the hypothesis that cholinergic systems play a greater role in the speed (but not accuracy) of performance of our learning and discrimination tasks compared to all other tasks. Accuracy of responding in these and the short-term memory task, all of which involve the use of lights as visual stimuli, was more sensitive to disruption by atropine than those tasks which did not utilize such strong visual stimuli.  相似文献   

2.
Increased knowledge of the cognitive abilities of mini-pigs is needed due to their increasing use in behavioral neuroscience research. Here, six female Yucatan mini-pigs performed tasks thought to measure timing behavior (temporal response differentiation, TRD), learning (incremental repeated acquisition, IRA), and motivation (progressive ratio, PR). Daily 30-min sessions for food reinforcers required a lever press be maintained for at least 10 but no longer than 14s (TRD), learning a new sequence of lever presses each test day (IRA) or an escalating number of presses for subsequent reinforcers (PR). All animals performed PR two days/week while three performed TRD five days/week and the other three performed IRA five days/week. Over the four test weeks, no animal completed TRD training and only one appeared to progress. For this task, lever press maintenance appeared difficult since by choice, the pigs used a front hoof, rather than the snout, to press the lever. IRA subjects showed gradually increasing performance with response rates comparable to those of rats but below those of children and monkeys and accuracy below that for rats. PR response rates were higher than those typically reported for rats, but lower than for adult rhesus monkeys or children. Physical differences in the way that each species responds likely account for these differences.  相似文献   

3.
The rat’s ability to vary its whisking “strategies” to meet the functional demands of a discriminative task suggests that whisking may be characterized as a “voluntary” behavior—an operant—and like other operants, should be modifiable by appropriate manipulations of response–reinforcer contingencies. To test this hypothesis we have used high-resolution, optoelectronic “real-time” recording procedures to monitor the movements of individual whiskers and reinforce specific movement parameters (amplitude, frequency). In one operant paradigm (N = 9) whisks with protractions above a specified amplitude were reinforced (Variable Interval 30?s) in the presence of a tone, but extinguished (EXT) in its absence. In a second paradigm (N = 3), rats were reinforced on two different VI schedules (VI-20s/VI-120s) signaled, respectively, by the presence or absence of the tone. Selective reinforcement of whisking movements maintained the behavior over many weeks of testing and brought it under stimulus and schedule control. Subjects in the first paradigm learned to increase responding in the presence of the tone and inhibit responding in its absence. In the second paradigm, subjects whisked at significantly different rates in the two stimulus conditions. Bilateral deafferentation of the whisker pad did not impair conditioned whisking or disrupt discrimination behavior. Our results confirm the hypothesis that rodent whisking has many of the properties of an operant response. The ability to bring whisking movement parameters under operant control should facilitate electrophysiological and lesion/behavioral studies of this widely used “model” sensorimotor system.  相似文献   

4.

Objective

Approximately 10% of young adults report non-medical use of stimulants (cocaine, amphetamine, methylphenidate), which puts them at risk for the development of dependence. This fMRI study investigates whether subjects at early stages of stimulant use show altered decision making processing.

Methods

158 occasional stimulants users (OSU) and 50 comparison subjects (CS) performed a “risky gains” decision making task during which they could select safe options (cash in 20 cents) or gamble them for double or nothing in two consecutive gambles (win or lose 40 or 80 cents, “risky decisions”). The primary analysis focused on risky versus safe decisions. Three secondary analyses were conducted: First, a robust regression examined the effect of lifetime exposure to stimulants and marijuana; second, subgroups of OSU with >1000 (n = 42), or <50 lifetime marijuana uses (n = 32), were compared to CS with <50 lifetime uses (n = 46) to examine potential marijuana effects; third, brain activation associated with behavioral adjustment following monetary losses was probed.

Results

There were no behavioral differences between groups. OSU showed attenuated activation across risky and safe decisions in prefrontal cortex, insula, and dorsal striatum, exhibited lower anterior cingulate cortex (ACC) and dorsal striatum activation for risky decisions and greater inferior frontal gyrus activation for safe decisions. Those OSU with relatively more stimulant use showed greater dorsal ACC and posterior insula attenuation. In comparison, greater lifetime marijuana use was associated with less neural differentiation between risky and safe decisions. OSU who chose more safe responses after losses exhibited similarities with CS relative to those preferring risky options.

Discussion

Individuals at risk for the development of stimulant use disorders presented less differentiated neural processing of risky and safe options. Specifically, OSU show attenuated brain response in regions critical for performance monitoring, reward processing and interoceptive awareness. Marijuana had additive effects by diminishing neural risk differentiation.  相似文献   

5.
To extend the investigation of tail-pinch induced behavioral changes, rats performing on a differential reinforcement of low rates of 10 sec (DRL10), a fixed-interval of 60 sec (F160), and a fixed-ratio of 20 (FR20) schedules were exposed to a paper clip applied to the tail. While a 10 min tail-pinch conducted 1 hr before operant sessions significantly altered the DRL10 behavior, this stressor had little effect on either F160 or FR20 responding. Marked DRL10 behavior performance changes following tail-pinch included increases in the number of lever presses, decreases in the number of the reinforcers, and disruption in the frequency distribution of inter-response times (IRT). These DRL10 operant deficits were diminished when the subject received a tail-pinch pretreatment followed by d-amphetamine treatment (0.2 and 2.0 mg/kg). In combination with biochemical data from others, the present results suggest that catecholamine systems are involved in modulation of DRL10 behavior following tail-pinch.  相似文献   

6.
This paper describes a novel method for studying the bio-behavioral basis of addiction to food. This method combines the surgical component of taste reactivity with the behavioral aspects of operant self-administration of drugs. Under very brief general anaesthesia, rats are implanted with an intraoral (IO) cannula that allows delivery of test solutions directly in the oral cavity. Animals are then tested in operant self-administration chambers whereby they can press a lever to receive IO infusions of test solutions. IO self-administration has several advantages over experimental procedures that involve drinking a solution from a spout or operant responding for solid pellets or solutions delivered in a receptacle. Here, we show that IO self-administration can be employed to study self-administration of high fructose corn syrup (HFCS). Rats were first tested for self-administration on a progressive ratio (PR) schedule, which assesses the maximum amount of operant behavior that will be emitted for different concentrations of HFCS (i.e. 8%, 25%, and 50%). Following this test, rats self-administered these concentrations on a continuous schedule of reinforcement (i.e. one infusion for each lever press) for 10 consecutive days (1 session/day; each lasting 3 hr), and then they were retested on the PR schedule. On the continuous reinforcement schedule, rats took fewer infusions of higher concentrations, although the lowest concentration of HFCS (8%) maintained more variable self-administration. Furthermore, the PR tests revealed that 8% had lower reinforcing value than 25% and 50%. These results indicate that IO self-administration can be employed to study acquisition and maintenance of responding for sweet solutions. The sensitivity of the operant response to differences in concentration and schedule of reinforcement makes IO self-administration an ideal procedure to investigate the neurobiology of voluntary intake of sweets.  相似文献   

7.
CCK-1-receptor-deficient Otsuka Long-Evans Tokushima fatty (OLETF) rats are hyperphagic and exhibit a greater preference for sucrose compared with lean controls [Long-Evans Tokushima Otsuka (LETO)]. To directly assess motivation to work for sucrose reward in this model of obesity and type 2 diabetes, we examined the operant performance of OLETF rats at nondiabetic and prediabetic stages (14 and 24 wk of age, respectively) on fixed-ratio (FR) and progressive-ratio (PR) schedules of reinforcement. To evaluate the involvement of dopamine systems, the effects of the D1 receptor antagonist SCH23390 (100 and 200 nmol/kg ip) and the D2 receptor antagonist raclopride (200 and 400 nmol/kg ip), were also tested on PR responding for sucrose. Compared with age-matched LETO rats, 14-wk-old OLETF rats emitted more licks on the "active" empty spout operant on the FR-10 schedule of reinforcement to obtain 0.01 M and 0.3 M sucrose and completed higher ratio requirements on the PR schedule to gain access to 0.3 M and 1.0 M sucrose. At 24 wk, this effect was limited to 1.0 M sucrose. Both antagonists were potent in reducing operant responding to 0.3 M sucrose in both strains at both ages, and there was no strain effect to SCH23390 at either age. OLETF rats, on the other hand, showed an increased sensitivity to the higher dose of raclopride, resulting in reduced responding to sucrose reinforcement at 24 wk. Taken together, these findings provide the first direct evidence for an increased motivation for sucrose reward in the OLETF rats and suggest altered D2 receptor regulation with the progression of obesity and prediabetes.  相似文献   

8.
The rat's ability to vary its whisking "strategies" to meet the functional demands of a discriminative task suggests that whisking may be characterized as a "voluntary" behavior--an operant--and like other operants, should be modifiable by appropriate manipulations of response-reinforcer contingencies. To test this hypothesis we have used high-resolution, optoelectronic "real-time" recording procedures to monitor the movements of individual whiskers and reinforce specific movement parameters (amplitude, frequency). In one operant paradigm (N = 9) whisks with protractions above a specified amplitude were reinforced (Variable Interval 30 s) in the presence of a tone, but extinguished (EXT) in its absence. In a second paradigm (N = 3), rats were reinforced on two different VI schedules (VI-20s/VI-120s) signaled, respectively, by the presence or absence of the tone. Selective reinforcement of whisking movements maintained the behavior over many weeks of testing and brought it under stimulus and schedule control. Subjects in the first paradigm learned to increase responding in the presence of the tone and inhibit responding in its absence. In the second paradigm, subjects whisked at significantly different rates in the two stimulus conditions. Bilateral deafferentation of the whisker pad did not impair conditioned whisking or disrupt discrimination behavior. Our results confirm the hypothesis that rodent whisking has many of the properties of an operant response. The ability to bring whisking movement parameters under operant control should facilitate electrophysiological and lesion/behavioral studies of this widely used "model" sensorimotor system.  相似文献   

9.
Habitual marijuana smoking is associated with inflammation and atypia of airway epithelium accompanied by symptoms of chronic bronchitis. We hypothesized that Delta(9)-tetrahydrocannabinol (THC), the primary psychoactive component of marijuana, might contribute to these findings by impairing cellular energetics and mitochondrial function. To test this hypothesis, we examined particulate smoke extracts from marijuana cigarettes, tobacco cigarettes, and placebo marijuana (0% THC) cigarettes for their effects on the mitochondrial function of A549 cells in vitro. Only extracts prepared from marijuana cigarettes altered mitochondrial staining by the potentiometric probe JC-1. With the use of a cross-flow, nose-only inhalation system, rats were then exposed for 20 min to whole marijuana smoke and examined for its effects on airway epithelial cells. Inhalation of marijuana smoke produced lung tissue concentrations of THC that were 8-10 times higher than those measured in blood (75 +/- 38 ng/g wet wt tissue vs. 9.2 +/- 2.0 ng/ml), suggesting high local exposure. Intratracheal infusion of JC-1 immediately following marijuana smoke exposure revealed a diffuse decrease in lung cell JC-1 red fluorescence compared with tissue from unexposed or placebo smoke-exposed rats. Exposure to marijuana smoke in vivo also decreased JC-1 red fluorescence (54% decrease, P < 0.01) and ATP levels (75% decrease, P < 0.01) in single-cell preparations of tracheal epithelial cells. These results suggest that inhalation of marijuana smoke has deleterious effects on airway epithelial cell energetics that may contribute to the adverse pulmonary consequences of marijuana smoking.  相似文献   

10.
Using a successive discrimination procedure with rats, three experiments investigated the contribution of reinforcement rate and amount of S(Delta) exposure on the acquisition of an operant discrimination. S(D) components and were always 2 min in length, while S(Delta) (extinction) components were either 1 min or 4 min in length; responses in S(D) were reinforced on one of four schedules. In Experiment 1, each of eight groups were exposed to one possible combination of rate of reinforcement and S(Delta) component length. At every level of reinforcement, the 4 min S(Delta) groups acquired the discrimination more quickly. However, within each level of reinforcement, the proportions of responding in S(D) as a function cumulative S(Delta) exposure were equivalent, regardless of the number of reinforcers earned in S(D), suggesting that extinction is the "hallmark" of discrimination. Experiment 2 sought to replicate these results in a within-subjects design, and although the 4 min S(Delta) conditions always produced superior discriminations, the lack of discriminated responding in some conditions suggested that stimulus disparity was reduced. Experiment 3 clarified those results and extended the finding that the acquisition of operant discrimination closely parallels extinction of responding in S(Delta). In sum, it appears that higher reinforcement rates and longer S(Delta) exposure facilitate the acquisition of discriminated operant responding.  相似文献   

11.
The Mathematical Principles of Reinforcement (MPR) model accurately predicts performance in fixed ratio (FR) schedules of reinforcement. The aim of the present study was to assess the generality of MPR with rats responding under progressive ratio (PR) schedules of different step sizes (PR1 or PR3) that provided either food or saccharin pellets. The results showed that the rats responding for saccharin pellets produced higher breakpoints (i.e., completed higher ratios) than those responding for food pellets. In terms of theoretical parameters, one finding unanticipated on the basis of MPR was that the a parameter (specific activation) was higher for the PR3 schedules. This finding suggests that specific activation may be affected indirectly by motor parameters of the task.  相似文献   

12.
Two measures of performance were used to study the effects of pulse-modulated microwave radiation (PM MWR) on schedule-controlled operant behavior of rats: 1) cued (SD), fixed-ratio (FR) bar pressing for food reinforcement; and 2) noncued (Sd) bar pressing in the absence of food reinforcement. The animals were irradiated and the behavioral data were obtained concurrently, during daily three-hour sessions, five days per week for six to nine weeks. Each experiment began with a two to three-week baseline interval of sham irradiation; a two to three-week interval of sham irradiation followed the irradiation phase. The irradiated animals were exposed to 1.3-Ghz PM MWR (pulse width of 1 microsecond at 600 pulses per second) at whole-body, average specific absorbed-dose rates of from 1.5–6.7 mW/g. Control and irradiated animals were tested in identical, cylindrical waveguide exposure/behavioral assemblies; different groups of irradiated and sham-irradiated animals were used for each dose rate. At 1.5 mW/g, the levels of SD operant responding by control and irradiated animals were comparable, and showed similar progressive diminutions over the course of each daily session. Sd operant responding was more variable, but again comparable, with both groups showing similar, progressive declines in rate of responding during each session. At 3.6 mW/g, no specific effects on SD operant response rates were observed. However, there was an initial and transient increase in the rate of extinction of Sd responding. At 6.7 mW/g, SD response rates were slightly reduced, whereas there was a major reduction in noncued (Sd) operant responding followed by a sharp rebound during the first post-MWR week. This marked reduction in Sd operant responding at MWR onset was in contrast to the relative stability and persistence of FR responding for food reinforcement.  相似文献   

13.
Squirrel monkeys were trained to respond under second-order schedules of food presentation and then sequentially exposed to either a self-administration (SA) and then a conditioned taste aversion (CTA) procedure, or a CTA procedure and then a SA procedure. Initial exposure to stimuli associated with post-session delivery of cocaine (0.3 mg/kg) either maintained (SA) or suppressed (CTA) responding, respectively. In contrast, following exposure to CTA, SA procedures failed to maintain levels of responding comparable to those seen with initial exposure to SA. Following exposure to SA, the CTA procedure failed to suppress responding. Thus, prior exposure to either the reinforcing or suppressant effects of cocaine modified its subsequent behavioral effects, suggesting a unique role for behavioral history in the abuse potential of cocaine.  相似文献   

14.
We investigated operant behavior in a novel species, the dwarf hamster (Phodopus campbelli). In two experiments, hamsters were trained to lever-press for food reinforcement. In Experiment 1, rate of reinforcement was manipulated across conditions using four variable-interval schedules of reinforcement (delivering one to eight reinforcers per min). As predicted, within-session decreases in responding were steepest on the richest schedule. In Experiment 2, lever-pressing was reinforced by either a constant or a variety of flavored food pellets. Within-session decreases in responding were steeper when the reinforcer flavor remained constant than when it was varied within the session. In both experiments, subjects hoarded most reinforcers in their cheek pouches rather than consuming them in the operant chambers. These results are incompatible with post-ingestive satiety variables as explanations for within-session decreases in operant responding and suggest that habituation to repeatedly presented reinforcers best accounts for subjects’ response patterns. Additionally, a mathematical model that describes behavior undergoing habituation also described the present results, thus strengthening the conclusion that habituation mediates the reinforcing efficacy of food.  相似文献   

15.
Britton KT  Akwa Y  Spina MG  Koob GF 《Peptides》2000,21(1):37-44
Central administration of neuropeptide Y (NPY) produces anxiolytic-like behavioral effects in rat models of anxiety. Because previous evidence has suggested a relationship between NPY and corticotropin-releasing factor (CRF) in the brain, we have focused on the interaction of these neuropeptide systems in emotional responsiveness to stressful stimuli. Intracerebroventricular administration of CRF produced a marked response suppression in an operant incremental shock conflict paradigm. NPY [(1 microg, intracerebroventricularly (i.c.v.)] significantly antagonized the response-suppressing effects of CRF (0.75 microg, i.c.v.) on punished responding in the conflict test at doses that produced little or no behavioral effect when administered alone. Central administration of the CRF antagonist [D-Phe(12), Nle(21,38),C(alpha) MeLeu(37)]CRF (D-Phe CRF(12-41)) alone did not alter punished or unpunished responding in the conflict test. However, pretreatment with the CRF antagonist before a subthreshold dose of NPY (1 microg, i.c.v.) produced a significant potentiation of the release of punished responding relative to NPY alone and untreated controls. NPY also antagonized the "anxiogenic-like" behavioral effects of CRF in the elevated plus maze. These findings support the hypothesis that NPY and CRF may reciprocally modulate an animal's behavioral response to stressful stimuli.  相似文献   

16.
Foods that are rich in fat and sugar significantly contribute to over-eating and escalating rates of obesity. The consumption of palatable foods can produce a rewarding effect that strengthens action-outcome associations and reinforces future behavior directed at obtaining these foods. Increasing evidence that the rewarding effects of energy-dense foods play a profound role in overeating and the development of obesity has heightened interest in studying the genes, molecules and neural circuitry that modulate food reward. The rewarding impact of different stimuli can be studied by measuring the willingness to work to obtain them, such as in operant conditioning tasks. Operant models of food reward measure acquired and voluntary behavioral responses that are directed at obtaining food. A commonly used measure of reward strength is an operant procedure known as the progressive ratio (PR) schedule of reinforcement. In the PR task, the subject is required to make an increasing number of operant responses for each successive reward. The pioneering study of Hodos (1961) demonstrated that the number of responses made to obtain the last reward, termed the breakpoint, serves as an index of reward strength. While operant procedures that measure changes in response rate alone cannot separate changes in reward strength from alterations in performance capacity, the breakpoint derived from the PR schedule is a well-validated measure of the rewarding effects of food. The PR task has been used extensively to assess the rewarding impact of drugs of abuse and food in rats (e.g., 6-8), but to a lesser extent in mice. The increased use of genetically engineered mice and diet-induced obese mouse models has heightened demands for behavioral measures of food reward in mice. In the present article we detail the materials and procedures used to train mice to respond (lever-press) for a high-fat and high-sugar food pellets on a PR schedule of reinforcement. We show that breakpoint response thresholds increase following acute food deprivation and decrease with peripheral administration of the anorectic hormone leptin and thereby validate the use of this food-operant paradigm in mice.  相似文献   

17.
Rates of responding by rats were usually higher during the variable interval (VI) 30-s component of a multiple VI 30-s fixed interval (FI) 30-s schedule than during the same component of a multiple VI 30-s VI 30-s schedule (Experiment 1). Response rates were also usually higher during the FI 30-s component of a multiple VI 30-s FI 30-s schedule than during the same component of a multiple FI 30-s FI 30-s schedule (Experiment 2). The differences in response rates were not observed when the components provided VI or FI 120-s schedules. These results were predicted by the idea that differences in habituation to the reinforcer between multiple schedules contribute to behavioral interactions, such as behavioral contrast. However, differences in habituation were not apparent in the within-session patterns of responding. Finding differences in response rates in both experiments violates widely-held assumptions about behavioral interactions, including that behavioral contrast does not occur for rats and that improving the conditions of reinforcement decreases, rather than increases, response rate in the alternative component.  相似文献   

18.
Summary SIRC cell monolayer cultures were exposed to whole smoke from a mid tar and nicotine level research cigarette (ASFC, 72 puffs), or from a high tar and nicotine level reference cigarette (Kentucky 2R1, 48 puffs) over a period of 65 days. The activity and distribution of lactate dehydrogenase (LDH) in the cells were investigated, and the electrophoretic characteristics of its isozymes studied. Cell morphology was examined by light microscopy and by transmission- and scanning electron microscopy.LDH activity was reduced by exposure to smoke from both cigarette types, the greater inhibitory effect being produced by that of the Kentucky cigarette. In addition, cells exposed to this high tar and nicotine smoke displayed intramitochondrial granules which were larger and more numerous than those found in cells exposed to the mid tar and nicotine smoke, or in the control cells. It is speculated that cation accumulation in the mitochondria may be involved in the observed inhibition of LDH activity.Supported by a research grant from the ASFC (Association Suisse des Fabricants de Cigarettes), Switzerland  相似文献   

19.
The term "sensory reinforcer" has been used to refer to sensory stimuli (e.g. light onset) that are primary reinforcers in order to differentiate them from other more biologically important primary reinforcers (e.g. food and water). Acquisition of snout poke responding for a visual stimulus (5s light onset) with fixed ratio 1 (FR 1), variable-interval 1min (VI 1min), or variable-interval 6min (VI 6min) schedules of reinforcement was tested in three groups of rats (n=8/group). The VI 6min schedule of reinforcement produced a higher response rate than the FR 1 or VI 1min schedules of visual stimulus reinforcement. One explanation for greater responding on the VI 6min schedule relative to the FR 1 and VI 1min schedules is that the reinforcing effectiveness of light onset habituated more rapidly in the FR 1 and VI 1min groups as compared to the VI 6min group. The inverse relationship between response rate and the rate of visual stimulus reinforcement is opposite to results from studies with biologically important reinforcers which indicate a positive relationship between response and reinforcement rate. Rapid habituation of reinforcing effectiveness may be a fundamental characteristic of sensory reinforcers that differentiates them from biologically important reinforcers, which are required to maintain homeostatic balance.  相似文献   

20.
Bilateral removal of the olfactory lobes in rats produces a number of behavioral, endocrine, and neurochemical alterations in the brain. Little is known, however, regarding the effects of this treatment on cardiovascular function and autonomic reflexes. Male Sprague-Dawley rats underwent bilateral surgical ablation of the olfactory bulbs (n = 10) or were sham operated (n = 8). After 3 wk of recovery, animals were instrumented with femoral catheters and a lumbar sympathetic nerve recording electrode. After 24 h of recovery, cardiovascular responses to arterial baroreflex manipulation, air jet stress, and smoke exposure were recorded. Olfactory bulbectomized rats demonstrated attenuated sympathoexcitatory responses to hypotension, air jet stress, and smoke exposure, as well as elevated basal blood pressure, compared with sham-operated rats. These data indicate that the integrity of the olfactory bulbs in rats is important for the elicitation of normal cardiovascular and autonomic responses to a number of evocative stimuli.  相似文献   

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