Sec Schedule Research Articles

Repeated Δ-9-Tetrahydrocannabinol administration dose dependently increases stablished schedule-induced drinking

RationaleSchedule-induced drinking (SID) reproduces an excessive and repetitive behavioural pattern that has led to propose this procedure as an animal model to study compulsive behaviours. Although it is known that cannabis can cause several adverse effects, in recent years there has been great interest in the medical application of cannabis derivatives for obsessive-compulsive related disorders.ObjectivesThe present study investigated the effects of repeated THC administration on rates of previously acquired SID, as well as the possible alteration of its temporal distribution along inter-food intervals.MethodsMale Wistar rats acquired SID under a 30 min fixed-time 30-sec food delivery schedule (from 30 to 43 sessions to reach a stable level). Thereafter, 5 or 10 mg/kg daily i.p. injections of THC or vehicle were repeatedly administered for 7 days to evaluate the effects on SID.ResultsRepeated THC administration at a dose of 5 mg/kg resulted in an increase on licking. Surprisingly, no effects on SID were observed with the 10 mg/kg dose. However, magazine entries were reduced with both THC doses. THC also modified the temporal distributions of licking and magazine entries during inter-food intervals.ConclusionsThe present results show that repeated THC administration may (i) increase induced licking at moderate doses, (ii) reduce magazine entries, and (iii) affect the temporal pattern of SID. These findings suggest that THC does not appear to be beneficial to reduce compulsive behaviour in this animal model, while another collateral effect of THC —such as a greater habitual-like behaviour— needs to be considered.

Ethanol→Nicotine & Nicotine→Ethanol drug-sequence discriminations: Conditional stimulus control with two interoceptivedrug elements in rats.

Self-administration of ethanol (E) and nicotine (N) occurs frequently in tandem orders (i.e., N→E vs. E→N) and thereby produces differing interoceptive profiles of subjective effects in humans. If the interoceptive stimulus characteristics of N→E differ from E→N, it is possible that such differences contribute to their co-dependence. The rationale for the present investigation was to determine whether ethanol, when preceded or followed by nicotine, produces different discriminative stimulus effects in rats. In two experiments, using a one-manipulandum operant drug discrimination procedure, rats were trained to discriminate temporal sequential administrations of ethanol (1.0g/kg) that was followed or preceded by nicotine (0.3mg/kg). Sessions alternated between food-reinforcement sessions on a variable interval 30-sec schedule (i.e., SD) and non-reinforcement sessions (i.e., SΔ). In Experiment 1, administrations of ethanol were followed or preceded by a 10-min interval of nicotine. Training sessions took place 10min following the second drug injection. Four groups of rats were trained to discriminate only one sequence from sequential administrations of saline, and each drug sequence was counterbalanced across groups for their roles as SD or SΔ. There was robust stimulus control. N→E and E→N functioned equally well as SD or SΔ. Experiment 2 used two groups of rats. For one group, the E→N sequence functioned as the SD and the N→E sequence functioned as the SΔ. The drug sequences were counterbalanced for the other group. Brief non-reinforcement tests revealed significantly greater responding during the SD sequence compared to the SΔ sequence for both groups. These results suggest that different drug sequences of ethanol followed or preceded by nicotine established reliable discriminative stimulus control over operant responding, potentially because of characteristic differences in the overlapping pharmacokinetic profiles of the NE compound. The results are discussed in terms of: 1) conditional stimulus control among two interoceptive drug states; and 2) the clinical modulation of human alcohol consumption and tobacco smoking.

Temporal specificity in Pavlovian-to-instrumental transfer.

Presentation of a previously trained Pavlovian conditioned stimulus while an organism is engaged in operant responding can moderate the rate of responding, a phenomenon known as Pavlovian-to-instrumental transfer. Although it is well known that Pavlovian contingencies will generate conditioned behavior that is temporally organized with respect to the arrival of the predicted outcome, little work has examined the temporal dynamics of responding during Pavlovian-instrumental transfer. We trained rats using a fixed time 60-sec, fixed time 120-sec, or random time 60-sec schedule in an appetitive Pavlovian task, and found that presentation of the conditioned stimulus potentiated operant responding in a manner that reflected these previously established temporal expectancies. Further, this temporal specificity conformed to the scalar property as seen with other forms of interval timing behavior. Surprisingly, this effect was only seen when the conditioned stimulus was a visual cue, but not when it was an auditory cue. These data suggest that the motivational processes triggered by Pavlovian cues are not static, but fluctuate in strength as a function of temporally specific expectations of reward.

Are Activist Investors Good or Bad for Business? Evidence from Capital Market Prices, Informed Traders, and Firm Fundamentals

We provide new evidence on the important and contentious question of whether interventions by activist investors add value to the targeted companies. Our large sample covers two decades and includes interventions in which the five-percent-ownership threshold for filing SEC Schedule 13D requires too much capital. We find that short-window returns around the public announcement are significantly positive and do not reverse in the post-intervention period; analyst recommendations decline prior to the intervention but increase significantly afterward; and short interest declines significantly in the post-intervention period. These favorable reactions are supported by significant improvements in target firms’ accounting fundamentals. Finally, ownership by long-term (“dedicated”) institutional investors increases after the intervention, and ownership by short-term (“transient”) investors decreases. Taken together, actions by informed market participants and accounting fundamentals provide consistent, strong evidence that investor activism strengthens the prospects of target firms.

A Need for Individual Data Analyses for Assessments of Temporal Control: Invertebrate Fixed Interval Performance

We outline several experimental variables and addressed the inconsistencies of these variables within the invertebrate fixed interval literature. We posit previous inconsistencies within the invertebrate fixed interval literature may be due to the utilization of aggregate versus individual analyses and contend individual analyses are critical in order for conclusions to be made about species’ abilities to emit responses that can come under temporal control. To exemplify these statements, we exposed honey bees Apis mellifera lingustica (N=13) to either an FI 15-sec or FI 30-sec schedule of reinforcement and analyzed subjects’ cumulative response records, response bin levels, quarter lives, inter-response time patterns, response duration patterns, and trial durations. No measures clearly indicated individual subjects’ responding came under temporal control of the fixed interval schedules; however, pooled group analyses did produce seemingly clear evidence of temporal control.

An assessment of fixed interval timing in free-flying honey bees (Apis mellifera ligustica): an analysis of individual performance.

Interval timing is a key element of foraging theory, models of predator avoidance, and competitive interactions. Although interval timing is well documented in vertebrate species, it is virtually unstudied in invertebrates. In the present experiment, we used free-flying honey bees (Apis mellifera ligustica) as a model for timing behaviors. Subjects were trained to enter a hole in an automated artificial flower to receive a nectar reinforcer (i.e. reward). Responses were continuously reinforced prior to exposure to either a fixed interval (FI) 15-sec, FI 30-sec, FI 60-sec, or FI 120-sec reinforcement schedule. We measured response rate and post-reinforcement pause within each fixed interval trial between reinforcers. Honey bees responded at higher frequencies earlier in the fixed interval suggesting subject responding did not come under traditional forms of temporal control. Response rates were lower during FI conditions compared to performance on continuous reinforcement schedules, and responding was more resistant to extinction when previously reinforced on FI schedules. However, no “scalloped” or “break-and-run” patterns of group or individual responses reinforced on FI schedules were observed; no traditional evidence of temporal control was found. Finally, longer FI schedules eventually caused all subjects to cease returning to the operant chamber indicating subjects did not tolerate the longer FI schedules.

Un método alternativo a la autocorrelación para analizar los efectos secuenciales de los programas de reforzamiento

It is known that fixed-interval schedules generate, at certain values, alt ernat ing short and Long postreinforcetnent pauses. TEtis effect has ben analyzed through autocorrelation methods with one-lag. However, this mnethods has shortcomings since it is unable to detect regularities in sequences of pauses that are non strictly cyclic. A computerprogram designed to assess cotnplex sequences of postreinforcement pauses is proposed. 1208 sequences of four pauses each, produced by a rat exposed to a fixed interval 60 sec schedule were analysed with tEtis alternative method. In agreement with previous reports. the analysis showed that alt cornbinotions of four pauses were equally lihely to occur.Cotnparisons of actual distributions of short and long pauses with a binornial distribu¬tion showed that 100% of total variance was accounted for. It was coneluded that dura¬tion of postreinforcement pause is a truly randotn event, at least for tEte conditions described Acre.

Stimulant effects of adenosine antagonists on operant behavior: differential actions of selective A2A and A1 antagonists

Adenosine A(2A) antagonists can reverse many of the behavioral effects of dopamine antagonists, including actions on instrumental behavior. However, little is known about the effects of selective adenosine antagonists on operant behavior when these drugs are administered alone. The present studies were undertaken to investigate the potential for rate-dependent stimulant effects of both selective and nonselective adenosine antagonists. Six drugs were tested: two nonselective adenosine antagonists (caffeine and theophylline), two adenosine A(1) antagonists (DPCPX and CPT), and two adenosine A(2A) antagonists (istradefylline (KW6002) and MSX-3). Two schedules of reinforcement were employed; a fixed interval 240-s (FI-240 sec) schedule was used to generate low baseline rates of responding and a fixed ratio 20 (FR20) schedule generated high rates. Caffeine and theophylline produced rate-dependent effects on lever pressing, increasing responding on the FI-240 sec schedule but decreasing responding on the FR20 schedule. The A(2A) antagonists MSX-3 and istradefylline increased FI-240 sec lever pressing but did not suppress FR20 lever pressing in the dose range tested. In fact, there was a tendency for istradefylline to increase FR20 responding at a moderate dose. A(1) antagonists failed to increase lever pressing rate, but DPCPX decreased FR20 responding at higher doses. These results suggest that adenosine A(2A) antagonists enhance operant response rates, but A(1) antagonists do not. The involvement of adenosine A(2A) receptors in regulating aspects of instrumental response output and behavioral activation may have implications for the treatment of effort-related psychiatric dysfunctions, such as psychomotor slowing and anergia in depression.

Concurrent VR VI schedules: Primacy of molar control of preference and molecular control of response rates

In the first condition in Experiment 1, 6 rats were exposed to concurrent variable ratio (VR) 30, variable interval (VI) 30-sec schedules. In the next two conditions, the subjects were exposed to concurrent VI VI schedules and concurrent tandem VI-differential-reinforcement-of-high-rate VI schedules. For the latter conditions, the overall and relative reinforcer rates equaled those in the first condition. Only minor differences appeared in time allocation (a molar measure) across conditions. However, local response rate differences (a molecular measure) appeared between schedule types consistently with the interresponse times these schedules reinforced. In Experiment 2, these findings reappeared when the prior experiment was replicated with 5 subjects, except that the VR schedule was replaced by a VI plus linear feedback schedule. These results suggest that within the context tested, the molar factor of relative reinforcement rate controls preference, whereas the molecular factor of the relation between interresponse times and reinforcer probability controls the local response rate.

Effects of GABAA Modulators in Rats Responding Under A Differential Reinforcement of Low Rates (DRL) Schedule

Little is known about the behavioral effects of neurosteroids in comparison to other drugs that modulate the GABAA receptor complex. The present study examined the effects of pregnanolone (1 – 10 mg/kg) and DHEA (32 – 240 mg/kg) in male rats responding under a DRL‐18 sec schedule of reinforcement. Lorazepam (0.01 – 3.2 mg/kg), ethanol (0.32 – 2.4 g/kg), pentobarbital (1.8 – 18 mg/kg), β‐CCM (0.32 – 5.6 mg/kg) and flumazenil (3.2 – 18 mg/kg) were tested for comparison, and pregnanolone was administered in combination with DHEA to determine if there were any antagonistic effects between these substances. Pregnanolone increased responding at intermediate doses and decreased responding at high doses similar to lorazepam, ethanol, and pentobarbital. All four drugs dose‐dependently decreased percent reinforced responding and shifted the response distribution curve downward and to the left. Dose‐effect curves were similar for DHEA, β‐CCM, and flumazenil, but different from those for the other four drugs (i.e., these drugs did not change response rate or shift the response distribution curve). DHEA did not antagonize the disruptive effects of pregnanolone on responding under this schedule. In summary, pregnanolone and DHEA produce effects on DRL responding similar to other drugs that modulate the GABAA receptor complex, and do not produce these effects through a single binding site. Supported by DA 019625

Role of Dopaminergic DAD1 and DAD2 Receptors in the Sensitization of Amphetamine-Suppressed Schedule-Induced Polydipsia in Rats

Effects of dopaminergic D1 (DAD1) and D2 (DAD2) receptors were examined in the sensitization of amphetamine (AMPH)-suppressed schedule-induced polydipsia (SIP). After training under a fixed-interval 60 sec schedule of food presentation in the presence of a water tube, rats received injections of different doses of AMPH 10 min prior to the test. It was found that AMPH at 2.0 mg/kg significantly to reduced licks and water intake during the SIP. The AMPH-suppressed SIP manifested again following 5-days of pretreatment with a sub-threshold dosage of AMPH (1.0 mg/kg) and a period of withdrawal. The role of dopaminergic D1 and D2 receptors was then examined by introducing D1 or D2 antagonist during the 5-days repeated injections of a sub-threshold dosage of AMPH. Results showed that DAD1 antagonist SCH23390 had little effect on the sensitization. However pretreatment with DAD2 antagonist haloperidol (HAL) prevented the sensitization to AMPH in the long-term rather than short-term withdrawal conditions. It is suggested that SIP could be a useful paradigm to study AMPH sensitization in rats and the involvement of dopamine receptors might be different.

Effects of free food deliveries and temporal contiguity on choice under concurrent-chain schedules

Eight pigeons responded in a concurrent chain with variable-interval (VI) 10-sec and VI 20-sec terminal links. Free food deliveries were then added to the initial links according to a variable-time (VT) 20-sec schedule in two conditions that differed in terms of whether a differential reinforcement of other (DRO) contingency was also arranged, which ensured that those deliveries could not occur within 2-sec of a response. Preference for the VI 10-sec terminal link increased when VT food was added, but not when the DRO contingency was operative, showing that free food deliveries affected preference only when those deliveries could be temporally contiguous with choice responding. This finding suggests that Mazur's (2003) report of increased preference with added VT food, replicated here, was due to adventitious reinforcement. Current models for behavioral choice are limited because they are based entirely on temporal relations between stimuli and reinforcers and fail to take into account response-reinforcer contiguity.

Response-cost punishment with pigeons: Further evidence of response suppression via token loss

Four pigeons responded on a two-component multiple token-reinforcement schedule, in which tokens were produced according to a random-interval 30-sec schedule and exchanged according to a variable-ratio 4 schedule in both components. To assess the effects of contingent token loss, tokens were removed after every second response (i.e., fixed-ratio 2 loss) in one of the components. Response rates were selectively lower in the loss components relative to baseline (no-loss) conditions, as well as to the within-condition no-loss components. Response rates were decreased to a greater degree in the presence of tokens than in their absence. To control for the effects of changes in the density of token and food reinforcement, two parts consisted of additional conditions where food density and token loss were yoked to those in a previous loss condition. In the yoked-food condition, tokens were produced as usual in both components, but the overall density of food reinforcement in one of the components was yoked to that obtained during a previous token-loss condition. In the yoked token-loss condition, tokens were removed during one component of the multiple schedule at a rate that approximately matched the obtained rate of loss from a previous token-loss condition. Response rates in these yoked components were less affected than those in comparable loss components, despite similar densities of token, exchange, and food reinforcement. On the whole, the results support the conclusion that contingent token loss serves as an effective punisher with pigeons.

The effects of signalled and unsignalled lick-dependent delays on the development of schedule-induced drinking in rats

Food pellets were programmed to be delivered to rats every 60 sec (Fixed Time 60-sec schedule), and the development of schedule-induced drinking was measured in terms of the amount of water consumed and the number of licks per inter-pellet interval. For some rats (masters) 10-sec delays in food delivery were dependent on licks. Yoked-control rats received food at the same time as their masters and independently of their own behaviour. In Experiment 1, in which the delays were signalled by a blackout, the master rats began to drink, but this schedule-induced behaviour then decreased to levels lower than those shown by the yoked controls. When the signalled delays were discontinued, the drinking of the master rats recovered. In Experiment 2, in which the delays were not signalled, the master rats did not develop as much schedule-induced drinking as the yoked controls, and discontinuing the delays led to only small increases in drinking. These results support the view that schedule-induced drinking is subjec...

Resurgence of behavior during extinction depends on previous rate of response

In two experiments, food-deprived rat subjects leverpressed for food in three successive training phases. In the first phase of both experiments, rats were exposed to a multiple schedule, one component of which produced a high rate of response, and the other of which produced a lower rate of response (multiple random ratio [RR], random interval [RI] in Experiment 1, and multiple differential reinforcement of high rate, differential reinforcement of low rate in Experiment 2). Rats were then transferred to a multiple fixed interval (FI; 60-sec, 60-sec) schedule, until the effects of the first phase on response rate were no longer apparent and their response rates did not differ from those of rats responding on a multiple FI 60-sec, FI 60-sec schedule without previously experiencing a multiple RR, RI schedule. During the third stage oftraining, all rats were placed into extinction. During extinction, rates of responding were higher in the component previously associated with the high rate of responding in Phase 1, and they were lower in the component previously associated with low rates of responding in Phase 1. These results suggest that resurgence effects, like other history effects, are controlled by previous rates of responding.

Remembering: The role of extraneous reinforcement

In two experiments, pigeons' responding on an extraneous task was explicitly reinforced during delayed matching-to-sample trials. In Experiment 1, red or green sample stimuli were followed by retention intervals of 0.2, 1, 4, or 12 sec, during which pecks to a white center key were reinforced with 2.5-sec access to wheat according to extinction, variable-interval 30-sec, and variable-interval 15-sec schedules in different conditions. A proportion of .2, .5, .7, or .9 of subsequent red or green choice responses that matched the sample were reinforced with 3-sec access to wheat. The result was that increasing center key reinforcement, or reducing reinforcer probability, lowered overall accuracy. Initial discriminability fell, but with no change in the rate of forgetting. In Experiment 2, initial discriminability was affected by extraneous reinforcers that were contingent on center key pecking, but not by noncontingent reinforcers. A plausible conclusion is that initial discriminability decreases when reinforcers strengthen competing behaviors.

Complex discriminative stimulus properties of (+)lysergic acid diethylamide (LSD) in C57Bl/6J mice

The drug discrimination procedure is the most frequently used in vivo model of hallucinogen activity. Historically, most drug discrimination studies have been conducted in the rat. With the development of genetically modified mice, a powerful new tool has become available for investigating the mechanisms of drug-induced behavior. The current paper is part of an ongoing effort to determine the utility of the drug discrimination technique for evaluating hallucinogenic drugs in mice. To establish the training procedures and characterize the stimulus properties of (+)lysergic acid diethylamide (LSD) in mice. Using a two-lever drug discrimination procedure, C57Bl/6J mice were trained to discriminate 0.45 mg/kg LSD vs saline on a VI30 sec schedule of reinforcement, with vanilla-flavored Ensure serving as the reinforcer. As in rats, acquisition was orderly, but the training dose was nearly five-fold higher for mice than rats. LSD lever selection was dose-dependent. Time-course studies revealed a rapid loss of the LSD stimulus effects. The 5-HT(2A/2C) receptor agonist, 2,5-dimethoxy-4-bromoamphetamine [(-)DOB] (1.0 mg/kg), substituted fully for LSD and the 5-HT(1A) receptor agonist, 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT) (1.6 mg/kg), substituted partially for LSD. Pretreatment with the 5-HT(2A) receptor-selective antagonist, MDL 100907, or the 5-HT(1A)-selective antagonist WAY 100635, showed that each antagonist only partially blocked LSD discrimination. Substitution of 1.0 mg/kg (-)DOB for LSD was fully blocked by pretreatment with MDL 100907 but unaltered by WAY 100635 pretreatment. These data suggest that in mice the stimulus effects of LSD have both a 5-HT(2A) receptor and a 5-HT(1A) receptor component.

Differential reinstatement predicted by preextinction response rate

Reinstatement refers to the recovery of previously extinguished responding by the response-independent delivery of a stimulus that was a reinforcer in training. Two experiments were conducted to examine relative reinstatement following the training of differential preextinction response rates, either with equal (Experiment 1) or unequal (Experiment 2) preextinction reinforcement rates. In Experiment 1, each of 3 pigeons first pecked at relatively high rates in the tandem variable-time 117-sec fixed-interval 3-sec component of a multiple schedule and at lower rates in a separate tandem variable-interval 117-sec fixed-time 3-sec component. Reinforcement rates were equal between components. Pecking then was extinguished in each component, before being reinstated under a multiple variable-time 120-sec variable-time 120-sec schedule. Greater reinstatement occurred in the component previously correlated with higher rates of pecking. In Experiment 2, in an initial condition, the mean rate of lever pressing for one group of 8 rats was significantly higher under a fixed-ratio 3 schedule than for another group of 8 rats under a fixed-ratio 1 schedule. Mean reinforcement rate was significantly higher for the group exposed to the fixed-ratio 1 schedule. For each group, lever pressing then was extinguished, before being reinstated under a variable-time 30-sec schedule. Significantly greater mean reinstatement occurred for the group previously exposed to the fixed-ratio 3 schedule. These results suggest that differential reinstatement may be predicted by preextinction response rate, perhaps independently of preextinction reinforcement rate.

Going Private - A Response to an Increased Regulatory Burden?

The directors and officers of many publicly held companies in the USA have been complaining that the regulatory requirements deriving from the Sarbanes-Oxley Act have become too burdensome for their companies. This paper includes an empirical study and discusses whether and to what extent publicly held companies in the USA have been taken private primarily because of the recently increased regulatory burden imposed on them. The study focuses on an analysis of a random sample of SEC Schedule 13E-3 going private filings in the year 2003. For the purpose of the analysis three categories of going private transactions have been distinguished: i) the Selection- or Clean-up-Transactions involving companies with fundamental problems, ii) the Undervaluation Transactions where a company or its controlling shareholder takes the company private to buy undervalued shares and realize a good business opportunity (typically leveraged-buy-out transactions), and iii) going private transactions for the primary purpose to avoid costs of being public. The study comes to the conclusion that most going private transactions in the year 2003 fall into the categories i) and ii). Thus, the statistic data on going private transactions does probably not support the statement that the regulatory requirements recently imposed on publicly held companies have become too burdensome.

Acquisition of schedule-induced polydipsia by rats in proximity to upcoming food delivery

Food-deprived rats that receive intermittent delivery of small amounts of food develop excessive drinking--specifically, schedule-induced polydipsia (SIP). A main characteristic of SIP is its occurrence at the beginning of interfood intervals. The purpose of this study was to demonstrate that SIP can be developed toward the end of interfood intervals, in closer proximity to upcoming than to preceding food delivery. In Experiment 1, two groups were exposed to a fixed-time (FT) 30-sec food schedule with water available during the first or the last 15 sec of each interfood interval. Two additional groups, which had access to water throughout, were exposed to FT 30-sec or FT 15-sec schedules of food presentation. The FT 30-sec group with free access to water developed the highest level of intake; similar and intermediate levels were induced in all the remaining groups. In Experiment 2, three groups of rats were exposed to an FT 90-sec food schedule with water available during the first, the second, or the last 30 sec of each interfood interval. One additional group with access to water throughout was exposed to the FT 90-sec schedule of food presentation. The group with free access to water developed a higher level of consumption than did the other groups, but by the end of training none of the four groups showed statistical differences in polydipsic drinking. Results show that adjunctive drinking can be developed in proximity to upcoming food delivery even with long interfood intervals.