Temporal Distribution Of Responses Research Articles

Cisplatin decreases voluntary wheel-running activity but does not impair food-motivated behavior in mice

Cisplatin is a chemotherapeutic agent that is still commonly used to treat solid tumors. However, it has several toxic side effects due in large part to the mitochondrial damage that it induces. As this mitochondrial damage is likely to result in a decrease in the amount of metabolic energy that is available for behavioral activities, it is not surprising that fatigue develops in cancer patients treated with cisplatin. The present preclinical study was initiated to determine whether the detrimental effects of cisplatin were more pronounced on physical effort requiring a lot of energy versus effort that not only requires less energy but also procures energy in the form of food. For this purpose, mice were either trained to run in a wheel or to work for food in various schedules of food reinforcement before being treated with cisplatin. The experiments were carried out only in male mice as we had already reported that sex differences in cisplatin-induced neurotoxicities are minimal. Cisplatin was administered daily for one cycle of five days, or two cycles separated by a five-day rest. As observed in previous experiments, cisplatin drastically reduced voluntary wheel running. In contrast, when cisplatin was administered to food-restricted mice trained to work for a food reward in a progressive ratio schedule or in a fixed-interval schedule, it tended to increase the number of responses emitted to obtain the food rewards. This increase was not associated with any change in the temporal distribution of responses during the interval between two reinforcements in mice submitted to the fixed interval schedule of food reinforcement. When cisplatin was administered to food-restricted mice trained in an effort-based decision-making task in which they had to choose between working for a grain pellet with little effort and working for a preferred chocolate pellet with more effort, it decreased the total number of responses emitted to obtain food rewards. However, this effect was much less marked than the decrease in wheel running induced by cisplatin. The decrease in the effort invested in the procurement of food rewards was not associated with any change in the relative distribution of effort between low reward and high reward during the time course of the test session. These findings show that cisplatin decreases energy-consuming activities but not energy-procuring activities unless they require a choice between options differing in their cost-benefit ratio. Furthermore, they indicate that the physical dimension of fatigue is more likely to develop in cisplatin-treated individuals than the motivational dimension of fatigue.

Confirmation of age-related alterations in inhibitory control using a modified minimally delayed oculomotor response (MDOR) task.

Considerable effort has been made to measure and understand the effects of ageing on inhibitory control using a range of behavioural tasks. In the minimally delayed oculomotor response (MDOR) task, participants are presented with a simple visual target step with variable target display duration (TDD), and instructed to saccade to the target not when it appears (a prosaccade response), but when it disappears (i.e., on target offset). Using this task, we recently found higher error rates and longer latencies for correct responses in older compared to younger participants. Here we have used a modified MDOR task, in which participants were presented with static placeholders identifying potential target positions (increasing spatial information), and three TDDs rather than two (reducing temporal predictability). We found that the yield of analysable trials was generally higher with this modified task and in 28 older (mean ± SD age: 65 ± 7 y) and 25 younger (26 ± 7 y) participants the total overall error rate was again higher in the older group (30 ± 18% vs. 16 ± 11%). An analysis of the temporal distribution of responses demonstrated a pronounced peak in error production around 150 ms (young) or 200 ms (old) after target onset. When we recalculated the error rate focusing on these errors, it was again significantly higher in the older group. The latency of correct responses (to offsets) was significantly increased in the older group, although much of this increase was accounted for by expected age-related visuomotor slowing. However, both latency and distribution data suggested that while older participants could generate increased levels of inhibition, they could not maintain these levels as efficiently as the younger participants. In 24 participants (15 old, 9 young) who completed both versions of the MDOR task, neither latency nor error rates differed significantly between versions. These results confirm an inhibitory control deficit in healthy older participants, and suggest that the dynamics of inhibitory control are also affected by ageing. The modified MDOR task yields more data while not altering basic performance parameters.

Parametric manipulations and fixed-interval self-stimulation

Three experiments investigated hypothalamic self-stimulation under a fixed-interval (FI) reinforcement schedule. An FI 20-s schedule was chosen to reduce stimulation density in order to minimize the influence of priming effects or stimulation aftereffects that can affect responding under other schedules of reinforcement. The first experiment showed that the influence of train duration is greatest at levels up to 1 s and thereafter level off over a wide range of train durations (1–32 s). The second experiment showed that altering frequency, current, or pulse width produced almost identical changes in FI responding. These findings show that the neutral network subserving hypothalamic self-stimulation simply integrates the amount of charge over time. It is relatively insensitive to the combination of stimulation parameters that make up a given waveform. In the third experiment, the chronaxies from the strength-duration curves indicate the neural substrate supporting self-stimulation has a great current-integrating capacity. Together, these experiments show that varying the amount of brain stimulation produce large and consistent changes in a number of FI response measures. These measures effectively describe different attributes of FI performance and include response rate, the postreinforcement pause, interresponse times of short duration and the temporal distribution of responses within the interval.

Enhanced resistance effect of piracetam upon hypoxia-induced impaired retention of fixed-interval responding in rats

Rats were trained on a fixed-interval schedule of 60 s (FI 60). After stabilization of performance, rats were chronically submitted to hypoxic treatment (3.5% O 2, 10 min) once a day, immediately after the daily FI 60 session. Hypoxia disturbed the retention of FI responding. It was mainly characterized by a decrease in response rate and in pause duration, and by changes in the temporal distribution of responses. Animals receiving piracetam (100 mg/kg, IP) 30 min before each FI session followed by hypoxia were significantly less affected than saline-treated animals. Results are discussed with reference to the effects of hypoxia and piracetam on nonspecific factors and on memory function. It is suggested that the effects of piracetam are due to alleviation of hypoxia-induced memory retrieval deficit rather than to a protection against hypoxic brain cell injury.

Effect of chronic hypoxic treatment on the retention of fixed-interval responding

The present experiments aimed to study the effects of hypoxic treatment (10 min on 3.5% oxygen) on the stabilized performance of rats in a fixed-interval schedule (FI 60 s). The hypoxic treatment was given once a day, for 3 days, immediately after the FI session. The results showed that the operant performance was disturbed from the very first posthypoxia FI session. There was a sharp drop in response rate, and changes in the temporal distribution of responses occurred. The data obtained greatly limit the importance of nonspecific factors in explaining these changes in performance. The results are discussed with reference to the retrieval hypothesis. In particular, it is suggested that the decreases of performance may be due to an effect of hypoxia on the retrieval mechanisms associated with long-term memory.

Effects of xylene isomers on operant responding and motor performance in mice

Xylene, a widely used industrial solvent, is a mixture of the ortho-, meta-, and para-isomers. In this study we examined the effects of each individual isomer, as well as a commercial-grade mixture of xylenes, on two behavioral measures: (1) operant performance of 15 mice trained to lever-press under a DRL (differential reinforcement of low rates) 10-sec schedule, and (2) motor performance of mice on an inverted screen test. The 15-min operant sessions immediately followed 30-min exposures to solvent vapors (500 to 7000 ppm), or air, in static inhalation chambers. All mice were exposed to each isomer in a counterbalanced order, and the mixture was given last in all cases. Ortho-, meta-, para-, and mixed xylenes produced similar biphasic effects on response rates, and concentration-dependent decreases in reinforcement rates. The lowest significantly effective concentration for each isomer on any variable was 1400 ppm, where increases in response rates occurred. Half-maximal response rate decreases were produced by 5179 ppm ( ortho-xylene) to 6176 ppm ( meta-xylene). The temporal distribution of responses was only moderately disrupted, even at high concentrations. In other groups of mice, motor coordination was also disrupted by the xylenes in a concentration-dependent manner. Half-maximal effective concentrations were 2676 ppm ( para-xylene) to 3790 ppm ( meta-xylene). Minimally effective concentrations were 2000 to 3000 ppm, higher than those seen in the operant studies. Xylene produced pronounced behavioral actions following acute exposure and no substantial differences in overall effects, and only slight potency differences, were obtained between the individual isomers or the commercial mixture.

Chlorpromazine effects on behavior under escape and fixed-time delivery of shock

Chlorpromazine has typically been found to reduce responding maintained by negative reinforcement. In squirrel monkeys, however, it has been shown to increase manipulative responses that occur just prior to shock presented under a fixed-time schedule. The present study compared chlorpromazine effects on behavior of rats under a fixed-time schedule of shock delivery and a schedule involving escape from shock. In all conditions, shock was delivered to the tail of rats held in partial restraint, and the response measured was displacement of a panel positioned directly in front of the rat's nose. The escape and fixed-time schedules generated similar temporal patterns and rates of responding under both schedules, and had no differential effect on the temporal distribution of responses within the shock-shock interval.

Contributions of stimulus-incentive and stimulus-response-incentive contingencies to response acquisition and maintenance

The effects of stimulus-incentive (S:IS) contingency, stimulus-response-incentive (S:R:IS) contingency, and stimulus-no-response-incentive (S:R:IS) contingency on the acquisition and maintenance of an instrumental approach-contact response in the rat were studied. The experiment, concerned mainly with the temporal distribution of responses, showed that (1) the S:IS contingency and the S:R:IS contingency produced the same temporal distribution of responses; (2) the S:R:IS contingency produced higher rates of response than the S:IS contingency; (3) the negative S:R:IS contingency did not completely eradicate already established responses; and (4)post-CS responding occurred on reinforced trials. Consideration of these results indicates that the critical factor determining the higher rates of response under the S:R:IS contingency may be the S:R:IS occasions experienced only in the instrumental procedure.