alpha7 Nicotinic acetylcholine receptors and temporal memory: synergistic effects of combining prenatal choline and nicotine on reinforcement-induced resetting of an interval clock

We previously showed that prenatal choline supplementation could increase the precision of timing and temporal memory and facilitate simultaneous temporal processing in mature and aged rats. In the present study, we investigated the ability of adult rats to selectively control the reinforcement-induced resetting of an internal clock as a function of prenatal drug treatments designed to affect the alpha7 nicotinic acetylcholine receptor (alpha7 nAChR). Male Sprague-Dawley rats were exposed to prenatal choline (CHO), nicotine (NIC), methyllycaconitine (MLA), choline + nicotine (CHO + NIC), choline + nicotine + methyllycaconitine (CHO + NIC + MLA), or a control treatment (CON). Beginning at 4-mo-of-age, rats were trained on a peak-interval timing procedure in which food was available at 10-, 30-, and 90-sec criterion durations. At steady-state performance there were no differences in timing accuracy, precision, or resetting among the CON, MLA, and CHO + NIC + MLA treatments. It was observed that the CHO and NIC treatments produced a small, but significant increase in timing precision, but no change in accuracy or resetting. In contrast, the CHO + NIC prenatal treatment produced a dramatic increase in timing precision and selective control of the resetting mechanism with no change in overall timing accuracy. The synergistic effect of combining prenatal CHO and NIC treatments suggests an organizational change in alpha7 nAChR function that is dependent upon a combination of selective and nonselective nAChR stimulation during early development.     

Differential reinforcement of low rates performance by impulsive and reflective children

Third-grade boys classified as either cognitively impulsive or reflective were reinforced for key pressing according to a DRL (differential reinforcement of low rates) 6-sec schedule of reinforcement. Half of each group received instructions about the behavioral requirements for obtaining reinforcements. Prior to DRL training, impulsive Ss showed a low probability of key press responding at long interresponse time (IRT) intervals while reflective Ss exhibited an equal probability of terminating either short or long IRTs. During training and in the absence of instructions, impulsives exhibited a less precise temporal discrimination, characterized by a greater predominance of response bursts (0–2 sec IRTs) following reinforcements, than reflective Ss. While impulsive and reflective Ss displayed similar frequencies of collateral behavior between successively reinforced responses, impulsives engaged in the reinforced response more frequently and tended (p < .08) to obtain fewer reinforcements. Instructions served to enhance the DRL performance.     

A developmental study of timing behavior in 4 1/2- and 7-year-old children

The present study investigated effects of age and instructions on temporal regulations of behavior in children. In the first experiment 4 1/2-year-old and 7-year-old subjects were trained with a DRL (differential reinforcement of low rates) 5-s and a DRL 10-s schedule. Results demonstrate that age and timing performance are related. Seven-year-olds are more efficient than the 4 1/2-year-olds. A striking decline in the 4 1/2-year-old children's capacity to space responses was observed in the DRL 10-s schedule as compared to the DRL 5-s schedule. Analysis of individual performances suggests that the evolution of DRL performance between 4 and 7 years of age depends not only on the development of the capacity to delay responding but also on the acquisition of the ability to represent the reinforcement contingencies, that is, the temporal parameters of the task to oneself. In order to test this hypothesis a second experiment was conducted where instructions to wait between operant responses were given to a group of 4 1/2-year-old subjects at the beginning of a DRL 5-s and a DRL 10-s schedule. The results show that these instructions enhance DRL performance. By directing the 4 1/2-year-old subjects' attention to the temporal requirements of the task, instructions led to efficient performance and accurate timing of responses to the DRL schedule.     

Effects of dl-amphetamine under concurrent VI DRL reinforcement

Three adult, food-deprived rats were given IP injections of dl-amphetamine sulfate under DRL and concurrent VI DRL reinforcement schedules. The drug results were as follows.(1) The IRT distributions of DRL responses shifted to the left, but some temporal discrimination remained. (2) The IRT distributions of VI responses shifted slightly to the left. (3) The distinguishing characteristics of VI and DRL IRT distributions were preserved. (4) The frequency distribution of number of VI responses between two consecutive DRL responses was relatively unaffected. (5) Over-all response rates on the two components of the concurrent schedules increased more or less proportionately.These findings imply that the primary behavioral effect of dl-amphetamine was a motor excitatory one. The drug's disruption of timing behavior was not due to a derangement of internal timing mechanisms, nor to interference with the topography or pattern of behavior. Rather, it might be a secondary result of the accelerated emission of overt behavior patterns mediating the temporal spacing of DRL bar presses.     

Discrimination of response-reinforcer and response-stimulus contingencies in pigeons

For three pigeons (Experiment 1), the presentation of a red response key ended with a food presentation either following two responses separated by at least 10 seconds (a DRL contingency) or following a 10-second response-free period (a DRO contingency). For three other birds (Experiment 2), a brief stimulus presentation terminated the DRL and DRO contingencies. A white side key was presented next and ended with response-dependent food following one contingency and a timeout following the other. Since the contingency on the red key was unsignaled, differential responding on the white side key could indicate that the two response-reinforcer relations had been discriminated. In Experiment 1, the red-key duration and number of responses influenced white-key responding following the contingency that predicted the timeout. A response-initiated DRO was instated, and the influence of red-key duration and response number on white-key responding was diminished. In both experiments, the 10-second time criterion in both contingencies was varied from 0.34 second to 10 seconds. Even at short time intervals the DRO and DRL contingencies were readily discriminated. Pigeons tended to class the two contingencies according to a rule that did not involve simply stimulus duration, numbers of responses, or even the time between a response and its consequence.     

Failure to acquire an inhibitory task following seizure-induced brain damage

Male rats that had displayed limbic seizures following a single pair of systemic injections of lithium and pilocarpine were trained 2 months later on an operant schedule that required differential low rates of responding (DRL). The seizured rats never acquired schedules that required either 6-sec. or 12-sec. inhibition of responses following a reward; these rats displayed more perseverative responding and shorter interresponse times than controls. Histomorphology indicated severe brain damage primarily within the entorhinal cortices (and adjacent amygdala) and dorsal thalamus.     

Drug effects on fixed-interval responding with pause requirements for food presentation.

In pigeons performing under a multiple schedule of food presentation, low key-pecking rates (0.18 to 0.29 responses per second) were maintained during 3-min fixed-interval components by requiring a 4-, 5-, or 6-sec pause preceding the food-delivery response (tandem DRL), while higher rates (0.70 to 1.37 responses per second) were maintained in alternative fixed-interval components by requiring a pause of no more than 40 msec preceding the food-delivery response (tandem DRH). Thus, reinforcement density was equal but overall response rates markedly different in the two schedule components. Pentobarbital (3, 10 mg/kg) had effects on overall rates of responding consistent with a rate-dependency interpretation (low rates were increased while higher rates were decreased), but d-amphetamine (0.03 to 3 mg/kg) either failed to increase low overall rates in the tandem DRL components or increased them only slightly. Effects of both drugs on local responding within the fixed-intervals were always related in an orderly way to control response rate, but the extent of rate increases produced by d-amphetamine was modifed in some birds by pause requirements such that the drug increased comparable rates less when these occurred in the tandem DRL component than when they occurred in the tandem DRH components. Control rate is an important determinant of drug effects, independent DRH components. Control rate is an important determinant of drug effects, independent of reinforcement density maintaining rates, and independent of environmental influences, such as response-spacing requirements for food presentation, that can modify the extent of some drug-produced rate changes.     

Conditioned suppression of drl responding: Effect of ucs intensity, schedule parameter, and schedule context

In Experiment I, groups of rats were trained to press a lever for food reinforcement on differential reinforcement of low rate (DRL) schedules which differed in parameter value. A stimulus which terminated with either a 0.5-mA or 2.0-mA electric shock was then superimposed upon each DRL baseline. In general, the magnitude of conditioned suppression was an inverse function of DRL schedule parameter and a direct function of shock intensity. Experiment II demonstrated that the rate of responding maintained by the DRL component of a multiple DRL-extinction schedule decreased during a stimulus preceding a 0.5-mA shock, whereas the rate of responding maintained by the DRL component of a multiple DRL-variable interval schedule showed little change or increased slightly during a stimulus preceding a 0.5-mA shock.     

Decreasing Excessive Bids for Attention in a Simulated Early Education Classroom

Differential-reinforcement-of-low-rate (DRL) schedules can be used to decrease, but not eliminate, excessive bids for teacher attention in a classroom. There are two primary methods of implementing a DRL: full session and spaced responding. Some research suggests that the full-session DRL may eliminate target responding. The purpose of the current study was to compare the effectiveness of and preference for the two DRL methods in a simulated preschool classroom. Three participants completed difficult puzzles in baseline, both DRL, and differential-reinforcement-of-other-behavior (DRO) conditions. In the spaced-responding and full-session DRL conditions, the optimal rate of bids for attention was approximately 75% (two participants) or 50% (one participant) of baseline responding. All participants requested attention near the optimal criterion in both DRL conditions and at a lower rate (near zero) in the DRO condition. Treatment preference of the students was assessed in a concurrent-chain arrangement. All participants preferred both types of DRL conditions to DRO, and two participants showed a preference for the full-session DRL. Results suggest that either DRL procedure may be suitable for a preschool classroom, but a full-session DRL may be ideal.     

Cholinergic blockade, septal lesions, and DRL performance in the rat.

Four experiments describing the effects of cholinergic blockade produced by systemic injection of either atropine sulfate or atropine methyl nitrate on the differential reinforcement of low rate (DRL) responding of rats are reported. It was shown that atropine sulfate injected either chronically or at high dosage suppressed DRL responding. Injected acutely, atropine sulfate produced disinhibitory effects. When atropine was injected either chronically or acutely into animals with septal lesions, there was suppression of responding. It was suggested that the specific behavioral outcome resulting from cholinergic blockade depends on the balance resulting from the competing peripheral and central effects of such blockade.     

Response suppression on DRL by rats with septal damage

The effectiveness of the differential reinforcement for low rates of responding (DRL) contingency in suppressing response rates of septal rats was investigated by using a Multi-DRL-yoked-VI (variable interval) schedule of reinforcement. The yoking procedure equated the interreinforcement times on the two schedules. Each schedule was in effect for half of each session, and the change in schedule was signaled by the presence or absence of a cue light. Schedule order and DRL delay requirement were varied. For both normal and septal rats, the response rates were higher in the VI component than the DRL component; this effect demonstrates that the responding of septals as well as normals is suppressed by the differential reinforcement of a particular class of IRTs. A sharp difference in the level of responding occurred at the point of transition from one component of the multiple schedule to the other, which provides evidence of a discrimination between the two schedules for both normals and septals. The conclusion is that the responding of septals is suppressed by the DRL contingency and not controlled solely by the density and distribution of reinforcement.     

Combined uridine and choline administration improves cognitive deficits in spontaneously hypertensive rats

Rationale. Hypertension is considered a risk factor for the development of cognitive disorders, because of its negative effects on cerebral vasculature and blood flow. Genetically induced hypertension in rats has been associated with a range of cognitive impairments. Therefore, spontaneously hypertensive rats (SHR) can potentially be used as a model for cognitive deficits in human subjects. Consecutively, it can be determined whether certain food components can improve cognition in these rats. Objective. The present study aimed to determine whether SHR display specific deficits in attention, learning, and memory function. Additionally, effects of chronic uridine and choline administration were studied. Methods. 5-7 months old SHR were compared with normotensive Wistar-Kyoto (WKY) and Sprague-Dawley (SD) rats. (a) The operant delayed non-matching-to-position (DNMTP) test was used to study short-term memory function. (b) The five-choice serial reaction time (5-CSRT) task was used to assess selective visual attention processes. (c) Finally, the Morris water maze (MWM) acquisition was used as a measure for spatial learning and mnemonic capabilities. Results. (1) SHR exhibited significantly impaired performance in the 5-CSRT test in comparison with the two other rat strains. Both the SHR and WKY showed deficits in spatial learning when compared with the SD rats. (2) Uridine and choline supplementation normalized performance of SHR in the 5-CSRT test. (3) In addition, uridine and choline treatment improved MWM acquisition in both WKY and SHR rats. Conclusion. The present results show that the SHR have a deficiency in visual selective attention and spatial learning. Therefore, the SHR may provide an interesting model in the screening of substances with therapeutic potential for treatment of cognitive disorders. A combination of uridine and choline administration improved selective attention and spatial learning in SHR.     

Choline Uptake in the Frontal Cortex Is Proportional to the Absolute Error of a Temporal Memory Translation Constant in Mature and Aged Rats

The relationship between the magnitude of the error in the content of temporal memory and sodium-dependent high-affinity choline uptake (SDHACU) in the frontal cortex and hippocampus was examined in mature (10- to 16-month-old) and aged (24- to 30-month-old) male rats. The peak time of the response rate distribution that relates the probability of a response to signal duration in a 20-s peak-interval timing procedure was used to index the remembered time of reinforcement. Regression analyses indicated that SDHACU in the frontal cortex of both mature and aged rats and in the hippocampus of aged rats is proportional to the absolute error in the content of temporal memory. These biochemical effects of peak-interval training were also compared with biochemical measures taken from control rats that received random-interval training. This comparison indicated that the observed changes in SDHACU were dependent upon the predictability of the programmed time of reinforcement and age-related changes in memory encoding and retrieval.     

DIFFERENTIALLY REINFORCING LOW RATES OF MISBEHAVIOR WITH NORMAL ELEMENTARY SCHOOL CHILDREN1

Effective nonpunitive procedures for reducing counterproductive classroom behaviors are of potential benefit to both students and teachers. A recent strategy for dealing with this class of problem behaviors involves the reinforcement of acceptably low levels of such behavior. The laboratory version of this procedure, called differential reinforcement of low rates of responding (or DRL), provides for a reinforcer to be delivered contingent upon a response that is separated from the last preceding response by a minimum amount of time. To make this procedure more amenable to classroom use, the present authors have modified it so that a reinforcer is delivered if fewer than a specified number of responses occur within a preset time interval (Deitz and Repp, Journal of Applied Behavior Analysis, 1973, 6 , 457–463). Previous studies using this procedure have found it effective in reducing and maintaining low rates of targeted behaviors. However, these effects have been demonstrated with groups of subjects and/or individuals from dependent populations. The present study investigated use of this modified DRL procedure with individual students in normal elementary classrooms. In the first of three studies, “talk-outs” of an 11-yr-old fifth-grade male were reduced when nonexchangeable gold stars were made contingent on two or fewer responses per session. During baseline sessions, an average of 4.45 talkouts were observed per 45-min session. Average responding subsequently fell to 1.83 when the modified DRL contingency was applied, increased to 7.60 during a reversal phase, and dropped again to an average of 1.20 when the contingency was reapplied. In the second study, out-of-seat behavior of a 12-yr-old sixth-grade female was reduced when gold stars were made contingent on two or fewer responses per 45-min class period. Baseline responding averaged 6.10 responses per session. When the contingency was applied, average responding fell to 0.16. During the reversal period, responding increased to an average of 6.00 and fell again, after the contingency was re-introduced to an average of 0.40. In the third study, a reduction in both talking-out and out-of-seat behaviors of another 11-yr-old fifth-grade male was demonstrated with a multiple-baseline design. Using different lengths of baselines, gold stars were made contingent first on a low rate of out-of-seat behavior, and then on a low rate of talk-outs. Out-of-seat responding fell from a baseline average of 7.50 to a treatment average of 1.14. Talk-outs went from a baseline average of 4.66 to a treatment average of 1.14. In all three studies, the modified DRL procedure proved effective with the children and was manageable by the classroom teacher. For the students, nonexchangeable conditioned reinforcers (stars) were sufficient to maintain lowered rates of inappropriate behavior with the modified DRL schedule; there was no need for an elaborate token economy, a process that in many cases may be only a form of behavioral “overkill”. As in other studies investigating DRL schedules, students were not informed of their accumulation of responses; the differential effects of providing or withholding this feedback need to be investigated. Overall, these studies add single-subject replication with normal children to the literature on modified DRL procedures.     

Effects of a DRL contingency added to a fixed-interval reinforcement schedule

Following 30 days of reinforcement for the bar press response of two white rats on 30-sec fixed-interval (FI), a DRL component was added so that a minimal interresponse time (IRT) for the reinforced response, in addition to the FI variable, was necessary for reinforcement. Marked control over response rate by the superimposed DRL requirement was demonstrated by an inverse hyperbolic function as the DRL component was increased from 1 to 24 sec within the constant 30-sec FI interval. Interresponse time and post-reinforcement (post-S^R) “break” distributions taken at one experimental point (DRL = 24 sec) suggested that a more precise temporal discrimination was initiated by an S^R than by a response, since the relative frequency of a sequence of two reinforced responses appeared greater than that of a sequence of a non-reinforced response followed by a reinforced one. This latter finding was confirmed with new animals in a follow-up experiment employing a conventional 24-sec DRL schedule.     

Effects of a brief novel stimulus during temporally spaced responding: Evidence for external inhibition?

Following training on schedules which differentially reinforce low rates of responding (DRL), three rats were exposed to a procedure to test for external inhibition. During test trials, a tone was presented midway in the DRL interval and the latency to the next response recorded. The incidence of external inhibition (defined in terms of the latency and its relative probability) appeared to be positively related to the size of the DRL schedule and not to measures of the subject’s “efficiency” on the schedule. An alternative view to the “pure” disinhibition hypothesis is presented which stresses the disruption of collateral behavior sequences which maintain responding under the DRL schedule.     

THE EFFECT OF CHANGES IN CRITERION VALUE ON DIFFERENTIAL REINFORCEMENT OF LOW RATE SCHEDULE PERFORMANCE

The differential reinforcement of low rate (DRL) schedule is commonly used to assess impulsivity, hyperactivity, and the cognitive effects of pharmacological treatments on performance. A DRL schedule requires subjects to wait a certain minimum amount of time between successive responses to receive reinforcement. The DRL criterion value, which specifies the minimum wait time between responses, is often shifted towards increasingly longer values over the course of training. However, the process invoked by shifting DRL values is poorly understood. Experiment 1 compared performance on a DRL 30‐s schedule versus a DRL 15‐s schedule that was later shifted to a DRL 30‐s schedule. Dependent measures assessing interresponse time (IRT) production and reward‐earning efficiency showed significant detrimental effects following a DRL schedule transition in comparison with the performance on a maintained DRL 30‐s schedule. Experiments 2a and 2b assessed the effects of small incremental changes vs. a sudden large shift in the DRL criterion on performance. The incremental changes produced little to no disruption in performance compared to a sudden large shift. The results indicate that the common practice of incrementing the DRL criterion over sessions may be an inefficient means of training stable DRL performance.     

Response timing variability: coherence of kinematic and EMG parameters

A detailed kinematic and electromyographic (EMG) analysis of single degree of freedom timing responses is reported to (a) determine the coherence of kinematic and EMG variability to the reduced timing error variability exhibited with amplitude increments within a given criterion movement time and (b) understand the temporal organization of various movement parameters in simple responses. The data reveal that the variability of kinematic (time to peak acceleration, duration of acceleration phase, time to peak deceleration) and EMG (duration of agonist burst, duration of antagonist burst, time to antagonist burst) timing parameters decreased with increments of average velocity in a manner consistent with the variable timing error. In addition, the coefficient of variation for peak acceleration, peak deceleration, and integrated EMG of the agonist burst followed the same trend. Increasing average movement velocity also led to decreases in premotor and motor reaction times. Overall, the findings suggest a strong coherence between the variability of response outcome, kinematic, and EMG parameters.     

AGGRESSION AS POSITIVE REINFORCEMENT IN MICE UNDER VARIOUS RATIO‐ AND TIME‐BASED REINFORCEMENT SCHEDULES

There is evidence suggesting aggression may be a positive reinforcer in many species. However, only a few studies have examined the characteristics of aggression as a positive reinforcer in mice. Four types of reinforcement schedules were examined in the current experiment using male Swiss CFW albino mice in a resident—intruder model of aggression as a positive reinforcer. A nose poke response on an operant conditioning panel was reinforced under fixed‐ratio (FR 8), fixed‐interval (FI 5‐min), progressive ratio (PR 2), or differential reinforcement of low rate behavior reinforcement schedules (DRL 40‐s and DRL 80‐s). In the FR conditions, nose pokes were maintained by aggression and extinguished when the aggression contingency was removed. There were long postreinforcement pauses followed by bursts of responses with short interresponse times (IRTs). In the FI conditions, nose pokes were maintained by aggression, occurred more frequently as the interval elapsed, and extinguished when the contingency was removed. In the PR conditions, nose pokes were maintained by aggression, postreinforcement pauses increased as the ratio requirement increased, and responding was extinguished when the aggression contingency was removed. In the DRL conditions, the nose poke rate decreased, while the proportional distributions of IRTs and postreinforcement pauses shifted toward longer durations as the DRL interval increased. However, most responses occurred before the minimum IRT interval elapsed, suggesting weak temporal control of behavior. Overall, the findings suggest aggression can be a positive reinforcer for nose poke responses in mice on ratio‐ and time‐based reinforcement schedules.     

Variable-interval schedules of timeout from avoidance: effects of chlordiazepoxide, CGS 8216, morphine, and naltrexone.

Rats were trained on concurrent schedules in which pressing one lever postponed shock and pressing the other occasionally (variable-interval schedule) produced a 2-min timeout during which the shock-postponement schedule was suspended and its correlated stimuli were removed. These procedures provided a baseline for studying the effects of drugs on behavior maintained by different sources of negative reinforcement (shock avoidance and timeout from avoidance). Experiment 1 studied a benzodiazepine agonist, chlordiazepoxide, and antagonist, CGS 8216. Chlordiazepoxide (2.5-30 mg/kg) had little effect on avoidance responding except at higher doses, when it reduced responding. By comparison, responding on the timeout lever was increased in 5 of 6 rats. These effects were reversed by CGS 8216 (2.5-5 mg/kg) in the 2 rats tested, but CGS 8216 had no effect by itself. Experiment 2 studied an opiate agonist, morphine, and antagonist, naltrexone, with 3 rats. Morphine's (2.5-20 mg/kg) effects were opposite those of chlordiazepoxide: At doses that either increased or had no effect on avoidance responding, morphine depressed timeout responding. Naltrexone (5 mg/kg) reversed these actions but had no effect by itself.