Response Rates Of Rats Research Articles

Una Exploración de las Propiedades Espaciales Desde la Lógica de los Programas de Estímulo

El objetivo de este trabajo fue explorar el efecto de variar la distancia espacial entre el bebedero y el conjunto luz-palanca sobre la ubicación espacial y la tasa de respuesta en ratas. Siguiendo la lógica de los programas temporales, se diseñó un experimento en el que una propiedad espacial (distancia) de los estímulos fue manipulada, mientras que las propiedades temporales se mantuvieron relativamente estables. El Grupo 1 fue expuesto a 3 fases en las que la distancia entre el bebedero y el conjunto luz-palanca fue aumentando. El Grupo 2 fue expuesto a condiciones similares, pero la distancia espacial fue disminuyendo. Al finalizar cada ciclo T de 30 s se entregó agua de forma contingente con una probabilidad de 1. Los sujetos fueron 8 ratas hembra de la cepa Wistar. Se emplearon cámaras de condicionamiento ampliadas en las que la ubicación espacial de los dispositivos de estimulación pudo cambiar. Los resultados mostraron que las ratas permanecieron más tiempo en la zona contigua al bebedero a pesar de que este cambiara de ubicación. También, se encontró que la tasa de respuesta mostró niveles bajos para todas las ratas a lo largo del experimento, no obstante, esta fue una función de la contigüidad espacial. Las pruebas no paramétricas de Wilcoxon y de U de Mann-Whitney fueron empleadas en el análisis estadístico. Se propone una serie de propiedades espaciales como la ubicación cardinal o la distribución geográfica que podrían ser estudiadas paramétricamente e integrarse en los programas de estímulo.

The effects of 100 dB 1‐kHz and 22‐kHz tones as punishers on lever pressing in rats

Aversive control is an important yet understudied process of learning. One reason aversive control may be relatively understudied is ethical concerns about painful stimuli (e.g., electric shock). High decibel broad-band noise and 22-kHz vocalizations both demonstrably affect rodent behavior while not necessarily being painful. The goal of this study was to determine if 100-dB 22-kHz-pure tones were differentially more effective in reducing operant response rates in rats. We examined whether 22-kHz pure tones would function as aversive stimuli, specifically as positive punishers. The effects of response-dependent as well as continuously presented 22-kHz and 1-kHz tones on rate of response maintained by variable interval 30-s food deliveries were assessed across several conditions. We found that response rates were lower when tones were presented response dependently than when tones were presented continuously throughout a session. We also found that the lower response rates obtained with response-dependent 22-kHz tones were not significantly different from response rates obtained with response-dependent 1-kHz tones. The primary conclusion of this experiment is that both 1-kHz and 22-kHz tones functioned as punishers, but that the 22-kHz tones were not differentially more effective in reducing response rate.

Early social isolation increases persistence of alcohol-seeking behavior in alcohol-related contexts.

Social conditions during rearing are well known to affect adult alcohol consumption, but few experiments have explored the effects of social conditions on behaviors that are related to alcohol dependence, such as the persistence of alcohol seeking. This study compared the effects of isolation (ISO) and interaction (INT) rearing on the persistence of alcohol-seeking behavior. Rats were trained to lever press for a solution of 10% alcohol diluted in water. They were then exposed to a two-component multiple schedule of reinforcement (baseline). Responses in one component were reinforced by a higher rate of alcohol delivery (rich component, variable interval 15 s) and responses in the other component were reinforced by a lower rate of delivery (lean component, variable interval 45 s). The persistence of lever pressing in the presence of each stimulus was then assessed during extinction. The results from baseline showed that response rates in rats in both groups were higher in the rich component than in the lean component, but ISO rats responded significantly more than INT rats in both components. The persistence of responding during extinction in ISO rats in both components was also higher than that in INT rats. The results show that effects of ISO are not restricted to alcohol consumption, but also affect persistence of alcohol-seeking behavior, which may reflect differences in the value of drug-related stimuli.

Response Rates Are Governed More by Time Cues Than Contingency

Classical conditioning is normally thought to strengthen associations between stimuli, and instrumental conditioning is thought to select responses. This difference has been used to account for the usual result that instrumental conditioning produces higher response rates than classical conditioning. The present experiment suggests that the comparison of instrumental and classical tasks has overlooked temporal cues that are often confounded with response contingency, and that the time cues exert a critical influence on response rate. When the two tasks are equated for temporal cues, the response rate of rats is similar in classical and instrumental tasks.

Within-session response rate in rats decreases as a function of amount eaten

AOYAMA, K. Within-session response rate in rats decreases as a function of amount eaten. PHYSIOL BEHAV 64(5) 765–769, 1998.—In past studies, within-session changes of rat feeding behavior were always treated as functions of time. This study aimed to describe the within-session decreases of operant response as a function of cumulative amount of food intake. Rats ( n = 8) were trained to obtain food pellets by lever-press responses. Session lengths were 45 min. The following results were observed: 1) Response rates during a CRF schedule were well described as a linear function of cumulative amount of food pellets eaten; 2) The linear equation was also accurate in describing the response rates during a semi-VI schedule; and 3) Even if schedules of reinforcement were changed within a single session, response rates in each reinforcement schedule were well described as linear functions of cumulative food intake. Thus, response rates decreased proportionally to the increase in cumulative amount of food intake.

SCHEDULE-CONTROLLED OPERANT BEHAVIOR OF RATS FOLLOWING ORAL ADMINISTRATION OF PERCHLOROETHYLENE: TIME COURSE AND RELATIONSHIP TO BLOOD AND BRAIN SOLVENT LEVELS

Previous studies have indicated that human exposure to perchloroethylene (PCE) produces subtle behavioral changes and other neurological effects at concentration at or below the current occupational exposure limit. Since comparable effects in animals may be reflected by changes in schedule-controlled operant behavior, the ability of orally administered PCE to alter fixed-ratio (FR) responding for a food reward was investigated in male Sprague-Dawley rats. Furthermore, since behavioral effects of solvents are likely to be more closely related to blood or target tissue (i.e, brain) concentrations than administered dose, the relationship between the pharmacokinetic distribution of PCE and its effects on operant responding was also evaluated. Rats trained to lever-press for evaporated milk on an FR-40 reinforcement schedule were gavaged with 160 or 480 mg/kg PCE and immediately placed in an operant test cage for 90 min. Separate animals gavaged with equivalent doses of PCE were used to determine profiles of blood and brain concentrations versus time. Perchloroethylene produced changes in responding that varied not only with dose but also among animals receiving the same dose. Changes in the response rates of rats receiving 160 mg/kg PCE were either not readily apparent, restricted to the first 5 min of the operant session, or attributable to gavage stress and the dosing vehicle. However, 480 mg/kg produced either an immediate suppression of responding for 15-30 min before a rapid recovery to control rates or a complete elimination of lever-pressing for the majority of the operant session. Although the two doses of PCE produced markedly different effects on operant behavior during the first 30 min of exposure, differences in brain concentrations of PCE were minimal. Furthermore, the majority of animals receiving 480 mg/kg PCE fully recovered from response suppression while blood and brain levels of the solvent continued to rise. Thus, relationships between blood and brain PCE levels and performance impairment were not discernible over the monitored time course. Since the rapid onset of response suppression suggests that the precipitating event occurs within the first few minutes of exposure, it is possible that altered responding is related to the rate of increase in blood or brain concentrations rather than the absolute solvent concentrations themselves. The relationship between the pharmacokinetic distribution of solvents and their effects on the central nervous system is obviously complex and may involve acute neuronal adaptation as well as the dynamics of solvent distribution among the various body compartments.

Midazolam's dose effects on fixed-ratio response rate in rats depend on amount of prior training experience.

Midazolam's dose effects on fixed-ratio response rate in rats depend on amount of prior training experience.

Midazolam's dose effects on fixed-ratio response rate in rats depend on amount of prior training experience.

Midazolam's dose effects on fixed-ratio response rate in rats depend on amount of prior training experience.

Effects of caffeine and PD 116,600 on the differential-reinforcement-of-low rate 72-S (DRL 72-S) schedule of reinforcement

Caffeine and PD 116,600 were found to decrease the reinforcement rate and increase the response rate in rats performing under a differential-reinforcement-of-low rate 72-s (DRL 72-s) schedule of reinforcement. In contrast, antidepressant drugs previously have been found to increase the reinforcement and decrease the response rate. Caffeine has been found to test similar to antidepressant drugs on at least one other behavioral screen, but caffeine does not possess clinical antidepressant properties. These results provide further support for the DRL 72-s schedule as a behavioral screen for antidepressant drugs.

Methocarbamol

The behavioural effects of methocarbamol, a centrally acting muscle relaxant, were assessed using self-injection procedures in baboons and drug discrimination procedures in baboons and rats. The ability of methocarbamol to maintain self-injection was examined using a drug substitution procedure. Responding was maintained initially by cocaine delivery (0.32mg/kg/injection, i.v.). Each drug injection was followed by a 3-h timeout allowing a maximum of eight injections per day. Methocarbamol doses or vehicle were substituted for cocaine for a period of 15 or more days each, with re-establishment of responding under cocaine after each substitution. Evaluation of a wide range of methocarbamol doses (1.0-32mg/kg/injection) showed that this compound maintained rates of self-injection at vehicle control levels, which were below those maintained by cocaine. The discriminative stimulus effects of methocarbamol were studied in baboons trained to discriminate either lorazepam (1.8mg/kg, p.o.) or pentobarbital (10.0mg/kg, p.o.) from the no-drug condition and in rats trained to discriminate lorazepam (1.0mg/kg, i.p.), diazepam (1.0mg/kg, i.p.), or pentobarbital (10.0mg/kg, i.p.) from the no-drug condition using a two-lever, food-maintained drug discrimination procedure. Evaluation of a range of doses in baboons (10-180mg/kg, p.o.) and rats (32-180mg/kg, i.p.) showed that methocarbamol did not occasion drug-lever responding at any dose. Methocarbamol did not produce changes in response rates in baboons, but higher doses severely suppressed response rates in rats. The present experiments show that the behavioral profile of methocarbamol is clearly distinguishable from that of barbiturates and benzodiazepines. Taken together with analogous studies with other sedative-anxiolytic drugs, these results suggest that methocarbamol has a relatively low likelihood of abuse.

Haloperidol produces within-session increments in operant response duration in rats

On the basis of previously reported observations that haloperidol induces within-session decrements in operant response rate in rats, it was suspected that other measures of operant behavior may also display within-session changes after treatement with this neuroleptic. Accordingly, haloperidol (0.02, 0.04, 0.08, 0.16 mg/kg) was administered to six rats trained on a fixed-ratio 20 schedule of liquid food reinforcement, and response duration was recorded as a measure of drug effects independent of response rate. Significant within-session decrements in response rate and increments in response duration were observed as responding ensued. At the 0.08 mg/kg dose, 300% increases in response duration were seen during the last third of the responses made in a session. The progressive slowing of individual motor acts were interpreted as neuroleptic-induced Parkinsonism in the rat, and within-session decrements in response rate were likewise seen as a manifestation of the same pharmacological effects that increased response duration.

Cholinergic involvement in the action of formetanate on operant behavior in rats

Formetanate (FMT) is a formamidine acaricide/insecticide with a carbamate moiety in its molecular structure. FMT-induced lethality is reportedly due to inhibition of acetylcholinesterase. Here we report evidence of the neurochemical basis for the sublethal, behavioral effects of FMT in rats. In this experiment, 0.5 mg/kg of FMT (5 min before the 55-min test session) produced a pronounced suppression of response rates in rats trained to lever-press under a multiple fixed-interval 1-min fixed-interval 5 min schedule of milk reinforcement. Injections of scopolamine (0.1 mg/kg) and methylscopolamine (0.1 mg/kg) 15 min before FMT blocked the response rate suppression, whereas pretreatment with either mecamylamine (2 mg/kg) or hexamethonium (2 mg/kg) did not. These data suggest that FMT acts as an indirect agonist on central and peripheral muscarinic receptors, by inhibiting acetylcholinesterase, to produce changes in schedule-controlled responding.

Effect of repeated intraperitoneal injections of soman on schedule-controlled behavior in the rat.

Intraperitoneal (IP) administration of the acetylcholinesterase inhibitor, soman (10-40 micrograms/kg), suppressed in a dose-related manner response rates in rats maintained under a multiple fixed-interval 50-s fixed-ratio 25 schedule of food delivery. Chronic administration of soman at weekly intervals resulted in tolerance to the response. When soman administration was separated by 2-5 weeks in individual rats, the suppressive effects of the agent again became apparent. Analysis of acetylcholinesterase activity revealed that enzyme inhibition was limited to gastrointestinal areas near the site of injection. There was no significant effect on brain acetylcholinesterase even following IP injection of doses which completely suppressed responding. The IP route may be useful for studying tolerance and other chronic effects of soman without producing generalized toxicity.

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.

Responding on a multiple schedule of reinforcement as a function of different septal lesions in the rat

The response rates of rats with either control operations or lateral, medial, or complete septal lesions were compared on a multiple fixed-interval (FI)/random-interval (RI) 40-sec schedule of reinforcement in which the rat was required to respond on a different lever for each alternating schedule component. Rats with lateral septal lesions responded at higher rates during the first 8-sec period of the FI component and had poorer response patterning than rats with control operations on the FI 40-sec reinforcement schedule. On the other hand, rats with medial septal lesions responded at higher rates than controls during the RI 40-sec component. Rats with complete septal lesions switched levers more than did controls before the ongoing schedule was completed. The results suggest that the lateral and medial septum have different functional roles mediating responding for food on interval schedules of reinforcement.

An examination of methodological refinements, clozapine and fluphenazine in the anhedonia paradigm

Previous work has shown that the reduction in operant response rate in rats treated repeatedly with pimozide is similar to the pattern of decline in rate occasioned by nonreward. This similarity, usually observed with a continuous reinforcement (CRF) schedule, has been interpreted in terms of the neuroleptics' reducing the rewarding quality of the reinforcer, i.e., anhedonia. Although retaining the CRF schedule, the present work departs from earlier methodologies in three major ways: retraining days were not interposed between drug or extinction days; the operant measure, response duration, was used to complement response rate in describing the drug and extinction effects; and, in addition to using pimozide (0.5 and 1.0 mg/kg), two other neuroleptics, clozapine (5.0 and 10.0 mg/kg) and fluphenazine hydrochloride (0.125 mg/kg), were examined in the anhedonia paradigm. Omission of the retraining days still resulted in declines in response rate and increases in response duration that were graphically similar for pimozide and extinction, but were significantly different in degree, with pimozide producing greater reductions in rate and lesser increases in duration than did extinction. Although clozapine, a low-motor-effect neuroleptic, reduced rate and elevated duration, no change was observed for repeated dosing at the 5.0 mg/kg dose level. The 10.0 mg/kg dose yielded a significant across-session increase (i.e., tolerance effect) in rates, an effect entirely the opposite of what would be indicative of anhedonia. Fluphenazine, a high potency, high-motor-effect phenothiazine, did produce a pattern of declining rate and increasing duration across the four days of dosing, and the 0.125 mg/kg of fluphenazine hydrochloride yielded greater effects than 1.0 mg/kg of pimozide. The extinction-like pattern of responding produced by fluphenazine and pimozide, but not by clozapine, suggests that anhedonia per se is insufficient to account for these results and that an as-yet-to-be-elucidated motor and/or associative process is involved.

Effects of inhalation exposures and intraperitoneal injections of methyl n-amyl ketone on multiple fixed-ratio, fixed-interval response rates in rats

Twelve rats were tested daily for 1 hr on a multiple fixed-ratio, fixed-interval schedule of reinforcement. The rats were given ip injections of methyl n-amyl ketone (MAK; 2-heptanone), an industrial solvent, in concentrations ranging from 18 to 175 mg/kg on one to eight occasions each, and were tested 15 min after the injections. When compared to the preceding control (saline) day, there was little or no fixed interval (FI) response rate change at 18 mg/kg, moderate FI rate decreases at 37 and 74 mg/kg and a near cessation of responding at 175 mg/kg MAK. Changes were statistically significant ( p<0.01) at 37, 74, and 175 mg/kg. The quantity of MAK which altered behavior was about 5% of the dose that was subsequently determined to be lethal to two-thirds of the test animals. Time course data indicated that the behavioral changes seen at 15 min after 175 mg/kg injections persisted for at least 1 hr but had vanished by 2.25 hr after the injections. Over the course of the study, there was a consistent reduction in the magnitude of the behavioral changes, suggesting that tolerance developed. Inhalation exposures below 1500 ppm did not cause behavioral changes, but those in excess of 1575 ppm had effects similar to the 175 mg/kg injections when testing began 5–10 min after termination of the inhalation exposure. However, a lack of opportunity for replications made it impossible to achieve statistical significance.

A BIOCHEMICAL‐BEHAVIORAL MODEL FOR STUDYING SEROTONERGIC SUPERSENSITIVITY IN BRAIN

AbstractChronic treatment with p‐chlorophenylalanine methylester (PCPA) resulted in enhanced sensitivity to D,L‐5‐hydroxytryptophan (5‐HTP) induced inhibition of response rates in rats working on a Variable Interval 1 min schedule of milk reinforcement. Marked depletions of 5‐hydroxytryptamine (5‐HT) were found in the cerebral cortex, hippocampus, striatum, diencephalon, mesencephalon, and pons‐medulla oblongata. Much smaller dopamine depletions were seen in some areas, particularly the hippocampus and pons‐medulla oblongata. Analysis of the binding of [3H]5‐HT to crude membrane fractions from the cerebral cortex of PCPA‐treated animals indicated a significant decrease in the apparent dissociation constant (KdAPP) for 5‐HT, but no change in the maximum binding capacity. The increased behavioral sensitivity to 5–HTP does not seem to be due to increased conversion of 5‐HTP to 5‐HT, increased uptake of 5‐HTP, or release of 5‐HT by p‐chlorophenylethylamine. However, the possibility that p‐chlorophenylalanine or the metabolite p‐chlorophenylacetic acid increased the binding of 5‐HT, thus decreasing KdAPP, cannot be ruled out. Some parallels between a recently proposed model of human depression and the observations of the present investigation are discussed.

The Effect of Methyl n-Butyl Ketone on Response Rates of Rats Performing on a Multiple Schedule of Reinforcement

The Effect of Methyl n-Butyl Ketone on Response Rates of Rats Performing on a Multiple Schedule of Reinforcement

Effects of combined treatment with nortriptiline and lorazepam on conflict behavior and motility of rats.

Lorazepam attenuated the suppressant effects of punishment on the response rate of rats in the multiple schedule of reinforcement devised by Geller and Seifter (1960). Nortriptiline alone was ineffective on punished responses. Both drugs, at certain dose levels, inhibited the nonpunished response. Combined treatment with the two drugs in a dose ratio of 1:20 attenuated the effects of punishment at all dose levels tested. The effects of the combination upon both punished and nonpunished responding was greater than might be accounted for by a simple additive effect of the individual treatments. Lorazepam and nortriptiline both induced a dose-related decrease in the locomotor activity of rats; when given together the 2 drugs antagonized each other. The results give an experimental support to the clinical observations about the usefulness of the benzodiazepine-antidepressant combination in certain depressive illnesses.