Effects of daily morphine administration and deprivation on choice and demand for remifentanil and cocaine in rhesus monkeys

Choice procedures have indicated that the relative reinforcing effectiveness of opioid drugs increases during opioid withdrawal. The demand curve, an absolute measure of reinforcer value, has not been applied to this question. The present study assessed whether mild morphine withdrawal would increase demand for or choice of remifentanil or cocaine. Four rhesus monkeys chose between remifentanil and cocaine during daily sessions. Demand curves for both drugs were subsequently obtained. The effects of daily injections of 3.2 mg/kg morphine on both choice and demand for these drugs was assayed 3 and 20.5 hr after each morphine injection, and then during a postmorphine period. Three hours following morphine injections, choice of remifentanil over cocaine decreased and demand for remifentanil--but not cocaine--became more elastic. During morphine withdrawal (20.5 hr postinjection), choice of remifentanil increased and remifentanil demand became more inelastic in 3 of 4 monkeys. Cocaine demand also became more inelastic during this period. Four to five weeks following the morphine regimen, demand for both drugs was more inelastic relative to the initial determination. The results suggest that both the relative and absolute reinforcing effectiveness of remifentanil decreased following morphine administration and increased during morphine withdrawal. The absolute reinforcing effectiveness of cocaine also increased during morphine withdrawal. In addition, extended exposure to drug self-administration and/or exposure to the morphine regimen produced long-term increases in demand for both drugs.     

Falsification of matching theory's account of single-alternative responding: Herrnstein's k varies with sucrose concentration

Eight rats pressed levers for varying concentrations of sucrose in water under eight variable-interval schedules that specified a wide range of reinforcement rate. Herrnstein's (1970) hyperbolic equation described the relation between reinforcement and responding well. Although the y asymptote, k, of the hyperbola appeared roughly constant over conditions that approximated conditions used by Heyman and Monaghan (1994), k varied when lower concentration solutions were included. Advances in matching theory that reflect asymmetries between response alternatives and insensitive responding were incorporated into Herrnstein's equation. After fitting the modified equation to the data, Herrnstein's k also increased. The results suggest that variation in k can be detected under a sufficiently wide range of reinforcer magnitudes, and they also suggest that matching theory's account of response strength is false. The results support qualitative predictions made by linear system theory.     

Differential outcome effect in the horse

Three horses were trained with a discrimination task in which the color (blue or yellow) of a center panel signaled the correct (left or right) response (lever press). Reinforcing outcomes for the two correct color-position combinations (blue-left and yellow-right) were varied across phases. Discrimination performance was better when the combinations were differentially reinforced by two types of food (chopped carrot pieces and a solid food pellet) than when the combinations were randomly reinforced by these outcomes or when there was a common reinforcer for each of the correct combinations. However, the discrimination performance established by the differential outcome procedure was still 80% to 90% correct, and an analysis of two-trial sequences revealed that the stimulus color of the preceding trial interfered with discrimination performance on a given trial. Our demonstration of the differential outcome effect in the horse and its further analysis might contribute to more efficient control of equine behavior in the laboratory as well as in horse sports.     

Effect of drugs on response-duration differentiation VII: response-force requirements

Rats were trained to press a lever for at least 1 s but for less than 1.3 s. The force required to press the lever was then increased or decreased by 10, 15, or 20 g. Increases in the force requirements for lever pressing decreased timing accuracy, but decreases in the force requirement had the opposite effect. Accuracy decreases at increasing force requirements were characterized by an increase in the relative frequency of responses that were too short to meet the reinforcement criterion. In contrast, increases in accuracy when the force requirements were decreased were characterized by increases in response durations that met the reinforcement criterion and decreases in the relative frequency of responses that were too short to produce the reinforcer. Phencyclidine (PCP) and methamphetamine produced dose-dependent decreases in accuracy that were associated primarily with increases in the relative frequency of short response durations, although methamphetamine also produced increases in long response durations at some doses. When the effects of PCP were determined with the force requirement increased by 10 g or decreased by 15 g, the cumulative response-duration distribution shifted toward even shorter response durations. When the effects of methamphetamine were determined with the force requirement on the lever increased by 10 g, the cumulative frequency distribution was shifted toward shorter response durations to about the same extent as it had been before force requirements increased; however, when the force required to press the lever was decreased by 15 g, these shifts toward shorter response durations almost completely disappeared. These results show that increases and decreases in the force requirements for lever pressing have different effects on the accuracy of temporal response differentiation.     

Studies of wheel-running reinforcement: parameters of Herrnstein's (1970) response-strength equation vary with schedule order

Six male Wistar rats were exposed to different orders of reinforcement schedules to investigate if estimates from Herrnstein's (1970) single-operant matching law equation would vary systematically with schedule order. Reinforcement schedules were arranged in orders of increasing and decreasing reinforcement rate. Subsequently, all rats were exposed to a single reinforcement schedule within a session to determine within-session changes in responding. For each condition, the operant was lever pressing and the reinforcing consequence was the opportunity to run for 15 s. Estimates of k and R(O) were higher when reinforcement schedules were arranged in order of increasing reinforcement rate. Within a session on a single reinforcement schedule, response rates increased between the beginning and the end of a session. A positive correlation between the difference in parameters between schedule orders and the difference in response rates within a session suggests that the within-session change in response rates may be related to the difference in the asymptotes. These results call into question the validity of parameter estimates from Herrnstein's (1970) equation when reinforcer efficacy changes within a session.     

Response induction during the acquisition and maintenance of lever pressing with delayed reinforcement

The acquisition of lever pressing by rats and the occurrence of unreinforced presses at a location different from that of the reinforced response were studied using different delays of reinforcement. An experimental chamber containing seven identical adjoining levers was used. Only presses on the central (operative) lever produced food pellets. Groups of 3 rats were exposed to one of seven different tandem random-interval (RI) fixed-time (FT) schedules. The average RI duration was the complement of the FT duration such that their sum yielded a nominal 32-s interreinforcement interval on average. Response rate on the operative lever decreased as the FT value was lengthened. The spatial distribution of responses on the seven levers converged on the operative lever when the FT was 0 or 2 s and spread across the seven levers as the FT value was lengthened to 16 or 32 s. Presses on the seven levers were infrequent during the FT schedule. Both operative- and inoperative-lever pressing intertwined in repetitive patterns that were consistent within subjects but differed between subjects. These findings suggest that reinforcer delay determined the response-induction gradient.     

Stimulus control and compounding with ambient odor as a discriminative stimulus on a free-operant baseline

Previous experiments have demonstrated that the simultaneous presentation of independently established discriminative stimuli can control rates of operant responding substantially higher than the rates occasioned by the individual stimuli. This "additive summation" phenomenon has been shown with a variety of different reinforcers (e.g., food, water, shock avoidance, cocaine, and heroin). Discriminative stimuli previously used in such studies have been limited to the visual and auditory sensory modalities. The present experiment sought to (1) establish stimulus control on a free-operant baseline with an ambient olfactory discriminative stimulus, (2) compare olfactory control to that produced with an auditory discriminative stimulus, and (3) determine whether compounding independently established olfactory and auditory discriminative stimuli produces additive summation. Rats lever pressed for food on a variable-interval schedule in the presence of either a tone or an odor, with comparable control developed to each stimulus. In the absence of these stimuli responding was not reinforced. During stimulus compounding tests, the tone-plus-odor compound occasioned more than double the responses occasioned by either the tone or odor presented individually. Thus, the current study (1) established stimulus control with an ambient olfactory discriminative stimulus in a traditional free-operant setting and (2) extended the generality of stimulus-compounding effects by demonstrating additive summation when olfactory and auditory discriminative stimuli were presented simultaneously.     

贯彻落实患者知情同意权刻不容缓

近年来,有关知情同意权方面的医疗纠纷在全部医疗纠纷事件中所占比重的逐年上升,贯彻落实知情同意权越发显得刻不容缓。本文着重从医疗管理角度出发,探讨如何做好相关宣传学习及完善相关制度。     

DISCRIMINATION OF VARIABLE SCHEDULES IS CONTROLLED BY INTERRESPONSE TIMES PROXIMAL TO REINFORCEMENT

In Experiment 1, food‐deprived rats responded to one of two schedules that were, with equal probability, associated with a sample lever. One schedule was always variable ratio, while the other schedule, depending on the trial within a session, was: (a) a variable‐interval schedule; (b) a tandem variable‐interval, differential‐reinforcement‐of‐low‐rate schedule; or (c) a tandem variable‐interval, differential‐reinforcement‐of‐high‐rate schedule. Completion of a sample‐lever schedule, which took approximately the same time regardless of schedule, presented two comparison levers, one associated with each sample‐lever schedule. Pressing the comparison lever associated with the schedule just presented produced food, while pressing the other produced a blackout. Conditional‐discrimination accuracy was related to the size of the difference in reinforced interresponse times and those that preceded it (predecessor interresponse times) between the variable‐ratio and other comparison schedules. In Experiment 2, control by predecessor interresponse times was accentuated by requiring rats to discriminate between a variable‐ratio schedule and a tandem schedule that required emission of a sequence of a long, then a short interresponse time in the tandem's terminal schedule. These discrimination data are compatible with the copyist model from Tanno and Silberberg (2012) in which response rates are determined by the succession of interresponse times between reinforcers weighted so that each interresponse time's role in rate determination diminishes exponentially as a function of its distance from reinforcement.     

Delay discounting in Lewis and Fischer 344 rats: steady-state and rapid-determination adjusting-amount procedures

Lewis rats have been shown to make more impulsive choices than Fischer 344 rats in discrete-trial choice procedures that arrange fixed (i.e., nontitrating) reinforcement parameters. However, nontitrating procedures yield only gross estimates of preference, as choice measures in animal subjects are rarely graded at the level of the individual subject. The present study was designed to examine potential strain differences in delay discounting using an adjusting-amount procedure, in which distributed (rather than exclusive) choice is observed due to dynamic titration of reinforcer magnitude across trials. Using a steady-state version of the adjusting-amount procedure in which delay was manipulated between experimental conditions, steeper delay discounting was observed in Lewis rats compared to Fischer 344 rats; further, delay discounting in both strains was well described by the traditional hyperbolic discounting model. However, upon partial completion of the present study, a study published elsewhere (Wilhelm & Mitchell, 2009) demonstrated no difference in delay discounting between these strains with the use of a more rapid version of the adjusting-amount procedure (i.e., in which delay is manipulated daily). Thus, following completion of the steady-state assessment in the present study, all surviving Lewis and Fischer 344 rats completed an approximation of this rapid-determination procedure in which no strain difference in delay discounting was observed.