Drug-behavior interaction history: modification of the effects of morphine on punished behavior.

Squirrel monkeys were trained to respond under a multiple fixed-interval, fixed-interval schedule in which the first response after 5 min terminated a visual stimulus in the presence of which electric shocks could occur. During one component of the schedule, correlated with one color of stimulus lights, every 30th response also produced electric shock; responding was suppressed during this component to approximately 10 to 12% of that occurring in the alternate component in which responding was not punished. In contrast to previous research, morphine (0.03 to 1.0 mg/kg) increased punished responding. Unpunished responding, however, was either not affected or decreased at doses of morphine that increased punished responding. Increases in rate of punished responding also occurred when the single-schedule punishment condition was studied alone in these animals. Subsequent experimentation, which systematically analyzed the development of the rate-enhancing effects of morphine on punished responding, involved the study of drug effects in additional monkeys trained initially under a single-schedule punishment condition. The effects of morphine on punished responding were studied before, after, and then during exposure to the multiple schedule that included a component in which responding was not punished. Increases in response rate with morphine did not occur until it was administered during exposure to the multiple schedule that included a component in which responding was not punished. As with the other monkeys, once the rate increases in punished responding occurred under the multiple schedule, these effects of morphine persisted, even when the multiple schedule was removed.(ABSTRACT TRUNCATED AT 250 WORDS)     

Unit price as a useful metric in analyzing effects of reinforcer magnitude.

In this paper, we applied the behavioral-economic concept of unit price to the study of reinforcer magnitude in an attempt to provide a consistent account of the effects of reinforcer magnitude on behavior. Recent research in the experimental analysis of behavior and in behavioral pharmacology suggests that reinforcer magnitude interacts with the schedule of reinforcement to determine response rate and total consumption. The utility of the unit-price concept thus stems from its ability to quantify this interaction as a cost-benefit ratio (i.e., unit price = characteristics of the schedule of reinforcement divided by magnitude of reinforcement). Research employing the unit-price concept has shown that as unit price increases, a positively decelerating function exists for consumption (i.e., a function with an increasingly negative slope, when plotted on log coordinates) and a bitonic function exists for response rate. Based on these findings, the present analysis applied the unit-price concept to those studies of reinforcer magnitude and drug self-administration that examined the effects of reinforcer magnitude on response rate using simple schedules of reinforcement (e.g., fixed-ratio schedule). This resulted in three findings: (a) Reinforcer-magnitude manipulations and schedule manipulations interact in a manner that can be quantified in terms of unit price as benefit and cost factors, respectively; (b) different reinforcer-magnitude manipulations are functionally interchangeable as benefit factors in the unit-price ratio; and (c) these conclusions appear warranted despite the differences in reinforcers (food or drug), species (dogs, monkeys, or rats), and schedules (interval or ratio), and despite the fact that these studies were not designed for a unit-price analysis. In methodological terms, these results provide further evidence that employing the unit-price concept is a parsimonious method for examining the effects of reinforcer magnitude. In theoretical terms, these results suggest that a single process may underlie the effect of combined reinforcer-magnitude and schedule manipulations.     

Sequential evaluation of behavioral treatments and methylphenidate dosage for children with attention deficit hyperactivity disorder

We used a sequential approach to evaluate the relative and combined effects of different types of behavioral treatments, as well as dosage of methylphenidate (MPH), on the disruptive behavior of 3 students who had been diagnosed with attention deficit hyperactivity disorder. Results showed that individualized behavioral treatments produced decreases in disruptive behavior equivalent to MPH for all 3 participants and demonstrated the need to evaluate behavioral treatments and medication dosage on an individual basis.     

遗传药理学发展史的哲学思考

遗传药理学是一门新兴学科,也是生命科学中发展迅速和备受关注的重要领域,在此领域我国处于世界先进水平。纵观遗传学中围绕发现基因的众多理论、药理学的产生发展和在此基础上的遗传药理学的发生和发展,让我们思考很多哲学问题,为我们科学地认识事物提供很多有益的启示。     

Low-dose caffeine discrimination and self-reported mood effects in normal volunteers.

A caffeine versus placebo discrimination procedure was used to determine the lowest caffeine dose that could produce discrimination and self-reported mood effects in normal volunteers. During daily sessions under double-blind conditions, caffeine-abstinent subjects orally ingested a capsule containing 178 mg caffeine or placebo. Before beginning discrimination training, the compounds were identified to subjects by letter codes. Fifteen, 30, and 45 min after capsule ingestion, subjects guessed the capsule's letter code. Correct guesses at 45 min earned money. After each session, subjects received a supplementary capsule containing caffeine or placebo to ensure that, within each phase of the study, subjects received the same daily dose of caffeine equal to the training dose. Five of the 15 subjects acquired the caffeine versus placebo discrimination within the first 20 sessions (greater than or equal to 75% correct); 6 other subjects acquired the discrimination with additional training. Nine subjects who acquired the discrimination were subsequently trained at progressively lower caffeine doses. In general, the lowest dose to produce discrimination (greater than or equal to 75% correct) was also the lowest dose to produce self-reported mood effects: 4 subjects showed discrimination and self-reported mood effects at 100 mg caffeine, 2 at 56 mg, 1 at 32 mg, and 1 at 18 mg. One of these subjects also showed self-reported mood effects at 10 mg. The present study documents discriminative stimulus and self-reported mood effects of caffeine at doses below those previously shown to affect any behavior in normal volunteers.     

Effects of income on drug choice in humans.

The effects of income (money available to spend during the experimental session) on human choice were examined in a concurrent-schedule arrangement. Subjects were 7 nicotine-dependent smokers, and reinforcers were puffs on the subject's usual brand of cigarette ("own") and puffs on a less preferred brand of cigarette with equal nicotine content ("other"). Across sessions, income varied and the price of the two reinforcers was held constant, with the other puffs one fifth the price of the own puffs. As income increased, consumption of own puffs increased while consumption of the less expensive other puffs decreased. These effects of income on choice were highly consistent across subjects. For some subjects, however, income had little effect on total puff consumption. Finally, an additional condition examined whether price and income manipulations would have functionally equivalent effects on choice by repeating an income condition in which the price of the other brand was increased. Although the increased price of the other puffs decreased their consumption in 4 subjects, 2 subjects showed increased consumption of the other puffs at the higher price. The results, when defined in economic terms, indicate that the own puffs were a normal good (consumption and income are directly related), the other puffs were an inferior good (consumption and income are inversely related), and the direct relationship between consumption of the other puffs and their price is defined as a Giffengood effect. The latter result also suggests that for these 2 subjects, price and income manipulations had equivalent effects on choice. These results extend findings from previous studies that have examined the effects of income on choice responding to human subjects and drug reinforcers, and provide a framework for further experimental tests of the effects of income on human choice behavior. Methodological and theoretical implications for the study of choice and for behavioral pharmacology are discussed.     

浅谈精神药理学的发展与相关哲学思考

如今精神疾病已成为中国严重的疾病负担,目前,精神障碍的治疗通常采用综合性措施,其中,药物治疗仍然占有重要地位。精神药理学是一门新兴学科,它的发展的确为许多精神、心理障碍的治疗带来了福音。精神药理学的发展史、当代进展与现状以及“个体化治疗”问题中都渗透着丰富的哲学思想,为我们科学地认识事物提供很多有益的启示。     

Comprehensive school-based behavioral assessment of the effects of methylphenidate.

Individualized assessments of the effects of three doses of methylphenidate (MPH) were conducted for 2 students with attention deficit hyperactivity disorder within each child's classroom using behavioral, academic, and social measures. A double-blind, placebo-controlled, multielement design was used to evaluate the results. Results suggested that at least one or more dosages of MPH were associated with some degree of improvement for both children in each area of functioning as compared to placebo. However, the degree of improvement at times varied substantially across dosage and area of functioning. Results suggest that MPH dosage and area of child functioning are critical assessment parameters and that controlled clinical trials are necessary to optimize the effectiveness of treatment with MPH for the individual child.