Discriminative stimulus effects of diazepam and buspirone in normal volunteers.

A within-subject design was used to characterize the effects of dose manipulations on discriminative and self-reported effects of oral diazepam and buspirone. Subjects were trained to discriminate diazepam (10 mg) versus placebo (n = 10), or buspirone (10 or 15 mg) versus placebo (n = 9). The compounds were identified to subjects by letter code before discrimination training began. In later sessions, correct identifications at 2 hr after the oral administration of drug earned money. All subjects showed accurate discrimination performance during the test-of-acquisition phase. In a low-dose generalization phase, diazepam and buspirone produced dose-related increases in drug identifications across a four-fold range of doses. In a subsequent low-dose training phase, in which subjects were trained to discriminate progressively lower drug doses, the median lowest discriminable dose of diazepam and buspirone was 2.5 and 7.5 mg, respectively. Dose-response functions for drug identifications were shifted leftward in the low-dose training phase relative to the low-dose generalization phase, suggesting that reinforcement of progressively lower doses enhances drug discriminability. The self-reported effects of diazepam and buspirone were similar (e.g., both drugs increased ratings of drug strength and clumsy/uncoordinated) and different (e.g., diazepam but not buspirone increased ratings of drowsy/sleepy; buspirone but not diazepam increased ratings of tense/nervous). This study demonstrates discriminative and self-reported effects of diazepam and buspirone at doses lower than previously shown to be behaviorally active, and suggests that at commonly used clinical doses, diazepam is relatively more discriminable than buspirone.     

A procedure for studying the within-session onset of human drug discrimination.

The purpose of the present study was to develop a procedure for measuring the within-session onset of human drug discrimination. During daily sessions, under double-blind conditions, caffeine-abstinent adults ingested a letter-coded capsule containing 178 mg caffeine or placebo. Trials were presented at 30-s intervals, beginning immediately after drug ingestion and continuing for 60 min. On each trial, subjects could guess which of their two letter-coded drugs they had received by pressing a left button (for one drug) or right button (for the other drug); subjects could also press a center "no guess" button instead of guessing. Each trial ended after one button press. After each session, subjects were told which drug they had received. Subjects earned one point (worth $0.10 per point) for each correct guess. Subjects lost either 0, 1, or 10 points for each incorrect guess; the point-loss contingencies were varied in random order across sessions. Discrimination earnings accumulated across all sessions. The point-loss contingencies decreased random responding and delayed the discrimination time course. Overall, this procedure provided an orderly and relatively continuous measure of the within-session onset of drug discrimination and should have a range of applications in understanding the human behavioral pharmacology of drugs.     

Caffeine effects on mood and memory.

The purpose of the present research was to assess whether a psychoactive dose of caffeine would have differential affects on the mood dimensions of arousal versus feelings of pleasantness and whether these mood alterations would influence memory either by (1) the experience of arousal at learning and/or (2) altered and congruent mood states at learning and recall. To address these questions, the administration of 5 mg/kg caffeine or placebo at learning and retrieval sessions was manipulated and subjects' mood was evaluated by several different self-report measures. Sixteen words were incidentally studied during the learning session and memory was evaluated by the number of words correctly recalled at the retrieval session two days later. Results revealed that caffeine reliably increased arousal, but did not affect any emotion dimensions related to feelings of pleasure. Subjects who received caffeine at learning and retrieval were also in equivalent mood states at both sessions. Moreover, caffeine did not produce any effects on memory; thus, neither hypothesis concerning the influence of arousal on memory was supported. These data show that caffeine is a useful method for manipulating arousal in the laboratory without influencing feelings of pleasantness or learning and memory performance.     

Haloperidol-induced Mood and Retrieval of Happy and Unhappy Memories

The present study investigated the effect of haloperidol-induced mood in normal healthy male volunteers on the retrieval of memories of real-life personal experiences using a between-subjects double-blind design. Forty subjects were required to retrieve past real life experiences associated with a series of stimulus words following administration of a single oral dose of 5mg haloperidol or placebo. The experiences were subsequently rated by subjects for their happiness felt at the time of the original experience. A significant decline in self-reported hedonic tone was observed in subjects given haloperidol. In addition, subjects on placebo recalled a significantly greater percentage of happy memories than subjects who were on haloperidol; a trend for a reverse pattern was observed for unhappy memories. The effects of the drug on the retrieval of memories were only in part mediated by the decline in hedonic tone scores. The effects of haloperidol are interpreted in terms of drug-induced dysphoria.     

Reinforcing effects of caffeine in coffee and capsules.

In a residential research ward the reinforcing and subjective effects of caffeine were studied under double-blind conditions in volunteer subjects with histories of heavy coffee drinking. In Experiment 1, 6 subjects had 13 opportunities each day to self-administer either a caffeine (100 mg) or a placebo capsule for periods of 14 to 61 days. All subjects developed a clear preference for caffeine, with intake of caffeine becoming relatively stable after preference had been attained. Preference for caffeine was demonstrated whether or not preference testing was preceded by a period of 10 to 37 days of caffeine abstinence, suggesting that a recent history of heavy caffeine intake (tolerance/dependence) was not a necessary condition for caffeine to function as a reinforcer. In Experiment 2, 6 subjects had 10 opportunities each day to self-administer a cup of coffee or (on different days) a capsule, dependent upon completing a work requirement that progressively increased and then decreased over days. Each day, one of four conditions was studied: caffeinated coffee (100 mg/cup), decaffeinated coffee, caffeine capsules (100 mg/capsule), or placebo capsules. Caffeinated coffee maintained the most self-administration, significantly higher than decaffeinated coffee and placebo capsules but not different from caffeine capsules. Both decaffeinated coffee and caffeine capsules were significantly higher than placebo capsules but not different from each other. In both experiments, subject ratings of "linking" of coffee or capsules covaried with the self-administration measures. These experiments provide the clearest demonstrations to date of the reinforcing effects of caffeine in capsules and in coffee.     

Discrimination of methadone and cocaine by pigeons without explicit discrimination training.

Pigeons were trained to peck a key on a variable-interval 2-min schedule of food reinforcement. Prior to each session, either 2.0 mg/kg methadone (n = 3), 3.0 mg/kg cocaine (n = 4), or 5.6 mg/kg cocaine (n = 2) was administered. When each pigeon's rate of pecking was stable, a range of doses of the training drug and saline were administered prior to 20-min extinction sessions separated by at least four training sessions. Rate of pecking during these extinction tests was generally an increasing function of dose, with the lowest rates obtained following saline and low doses and the highest rates obtained following doses near the training doses. Dose functions from pigeons trained with 5.6 mg/kg cocaine were steeper than those from pigeons trained with 3.0 mg/kg cocaine. Pigeons trained with methadone or 3.0 mg/kg cocaine were then given discrimination training, in which food reinforcement followed drug administration and 20-min extinction sessions followed saline administration. Rates of pecking under these conditions quickly diverged until near-zero rates were obtained following saline and high rates were obtained following drug. Discrimination training steepened dose functions for the training drugs, and the effects of several other substituted drugs depended on the pharmacology of the training drug. The pigeons trained with 5.6 mg/kg cocaine were tested with d-amphetamine, methadone, and morphine prior to discrimination training. d-Amphetamine increased rates dose dependently, and methadone and morphine did not. The results suggest that discriminative control by methadone and cocaine was established without explicit discrimination training.     

Effect of caffeine on motor performance by caffeine-naive and -familiar subjects.

The purpose of this investigation was to assess the effect of caffeine on selected manipulation skills by caffeine-naive and caffeine-familiar subjects. The subjects were 20 caffeine-naive (less than 90 mg/d) and 20 caffeine-familiar (greater than 750 mg/d) college-age (21 +/- 1.7 yr.) women. Measurements included steadiness error time and frequency, duration of tracing, error time and frequency, and dexterity. Doses of 2.5, 5.0 mg.kg-1 body weight caffeine or a placebo (200 mg. methylcellulose) were administered randomly to all subjects on three separate occasions. A 2 x 3 repeated-measures analysis of variance yielded a significant group difference for steadiness error time between the 5 mg.kg-1 and 2.5 mg.kg-1 dose and between 5 mg.kg-1 and the placebo. For frequency of steadiness errors, the nonuser group posted significant gains for both 5.0 and 2.5 mg.kg-1 over the placebo control. On tracing error time and error frequency, 5.0 mg.kg-1 resulted in significant increases from both 2.5 mg.kg-1 and the placebo group. In the caffeine-naive group, both doses of caffeine led to significant increases in dexterity time from the placebo, and the 5.0 mg.kg-1 dose was significantly different from the 2.5 mg.kg-1 trial. It was concluded that caffeine had detrimental effects on selected performance skills of caffeine-naive women but not in caffeine-familiar women.     

Cardiovascular reactivity, mood, and task performance in deprived and nondeprived coffee drinkers

Forty habitual, heavy coffee drinkers (M = 5.7 cups/day) participated in two experimental sessions. Participants were deprived of their morning coffee for one of the laboratory sessions, not deprived the other. During each session, subjects consumed 12 oz of caffeinated coffee, decaffeinated coffee, or caffeine-free herbal tea. Measurements of heart rate, blood pressure, mood, and catecholamine response to deprivation and consumption of the beverage, alone and in combination with challenging tasks, were made. This study found that caffeine continues to cause blood pressure increases with chronic, heavy consumption and that these effects do not appear to habituate with regular use. Subjects reacted to behavioral challenge with fewer negative mood effects if they had consumed caffeine or coffee. Mild caffeine deprivation was associated with symptoms of stress.     

Mood influences on acute smoking responses are independent of nicotine intake and dose expectancy

Acute responses to smoking are influenced by nicotine and by nonpharmacological factors such as nicotine dose expectancy and sensory effects of smoke inhalation. Because negative mood increases smoking reinforcement, the authors examined whether these effects may be altered by mood context. Smokers (n=200) participated in 2 sessions, negative or positive mood induction, and were randomized to 1 of 5 groups. Four groups comprised the 2x2 balanced placebo design, varying actual (0.6 mg vs. 0.05 mg yield) and expected nicotine dose (expected nicotine vs. denicotinized [denic]) of cigarettes. A fifth group was a no-smoking control. Smoking, versus not smoking, attenuated negative affect, as well as withdrawal and craving. Negative mood increased smoking reinforcement. However, neither actual nor expected nicotine dose had much influence on these responses; even those smokers receiving and expecting a denic cigarette reported attenuated negative affect. A follow-up comparison suggested that the sensory effects of smoke inhalation, but not the simple motor effects of smoking behavior, were responsible. Thus, sensory effects of smoke inhalation had a greater influence on relieving negative affect than actual or expected nicotine intake.     

Percolating ideas: The effects of caffeine on creative thinking and problem solving

Caffeine is the most widely consumed psychotropic drug in the world, with numerous studies documenting the effects of caffeine on people’s alertness, vigilance, mood, concentration, and attentional focus. The effects of caffeine on creative thinking, however, remain unknown. In a randomized placebo-controlled between-subject double-blind design the present study investigated the effect of moderate caffeine consumption on creative problem solving (i.e., convergent thinking) and creative idea generation (i.e., divergent thinking). We found that participants who consumed 200 mg of caffeine (approximately one 12 oz cup of coffee, n = 44), compared to those in the placebo condition (n = 44), showed significantly enhanced problem-solving abilities. Caffeine had no significant effects on creative generation or on working memory. The effects remained after controlling for participants’ caffeine expectancies, whether they believed they consumed caffeine or a placebo, and changes in mood. Possible mechanisms and future directions are discussed.     

Effect of drugs on human discrimination ability

The effects of phenobarbital, nitrazepam, diazepam, medazepam, chlordiazepoxide, phenytoin, carbamazepine, thioridazine and caffeine on the detail discrimination ability of healthy subjects were compared with those of a placebo by means of the d2-test and the Bourdon-Wiersma test. The impairment of performance induced by phenobarbital, thioridazine and diazepam varied with dosage. The improved performance yielded by caffeine was related to both dose and time. Both deletion tests yielded the same results. They are suitable for detecting the effects of drugs and have proved useful for clinicopharmacological and clinicopharmacological and clinicopsychopharmacological studies.     

Comparing single and cumulative dosing procedures in human triazolam discriminators.

This study evaluated a cumulative dosing procedure for drug discrimination with human participants. Four participants learned to discriminate triazolam (0.35 mg/70 kg) from placebo. A crossover design was used to compare the results under a single dosing procedure with results obtained under a cumulative dosing procedure. Under the single dosing procedure, a dose of triazolam (0, 0.05, 0.15, or 0.35 mg/70 kg) or secobarbital (0, 25, 75, or 175 mg/70 kg) was administered 45 min before assessment. Determining each dose-effect curve thus required four sessions. Under the cumulative dosing procedure, four doses of triazolam (0, 0.05, 0.10, and 0.20 mg/70 kg) or secobarbital (0, 25, 50, and 100 mg/70 kg) were administered approximately 55 min apart, producing a complete dose-effect curve in one four-trial session. Regardless of procedure, triazolam and secobarbital produced discriminative stimulus and self-reported effects similar to previous single dosing studies in humans. Shifts to the right in cumulative dose-effect curves compared to single dose-effect curves occurred on several self-report measures. When qualitative stimulus functions rather than quantitative functions are of interest, application of cumulative dosing may increase efficiency in human drug discrimination.     

State-dependent recall decrements with moderate doses of alcohol

Thirty-two adult volunteers were asked to memorize a simplified geographical map, visually displayed, together with an auditorially presented 19-item set of instructions regarding a particular route. During this session, half the subjects were sober and half were under the effects of a moderate dose of alcohol (mean blood alcohol concentration = 81mg/100ml). Twenty-four hours later they were tested under the same or different conditions. Learning performance on Day 1 was unaffected by alcohol. Learning transfer (tested on Day 2) was equally good when subjects were intoxicated during both sessions or were sober during both sessions. There were significant decrements in recall on Day 2, when subjects were in a different drug state. This ‘dissociation of learning’ was found to be symmetrical in that the recall decrement was the same whether the initial learning was acquired in a sober or a drugged state.     

Impact of caffeine and psychological stress on blood pressure in black and white men

The purpose of this study was to examine the effects of caffeine and psychological stress on systolic blood pressure (SBP) and heart rate (HR) in 40 healthy Black and White male regular coffee drinkers. Half the subjects had a positive family history of hypertension (FH+), and half did not. The effects of 250 mg of caffeine versus placebo (3 mg) in decaffeinated coffee were compared in a within-subject, double-blind, cross-over design. SBP and HR were measured at rest, after caffeine ingestion, during mental arithmetic stress, and during recovery. Results confirmed previous findings with White men that a moderate dose of caffeine produced significant increases in SBP and little effect on HR and that the pressor effects of caffeine and stress combined additively. Contrary to expectations, no overall race or family history differences in SBP levels or in SBP reactivity were observed. FH+ Blacks, however, evidenced slower SBP recovery than Whites. Whites evidenced higher overall HR levels than blacks, but this difference was not specific to caffeine or to mental stress. Mechanisms of racial differences in reactivity underlying differential risk for hypertension are discussed, as well as the utility of caffeine as a pharmacologic probe for such differences.     

Effects of caffeine on performance of low intensity tasks

31 college age men and women who consume less than three caffeinated beverages per week agreed to participate as subjects in research on the effects of acute caffeine intake on low intensity task performance. All subjects performed two randomly administered test conditions: (1) caffeine (5 mg/kg) and (2) placebo on separate visits following an initial 1-hr. orientation visit. Subjects were administered the beverage 30 min. prior to performing 12 separate tests assessing basic mathematics, simple response, logical reasoning, hand-eye coordination, and spatial and assembly skills. The Spielberger State Anxiety test was administered immediately after consuming the test beverage and once again at posttest. Analysis showed that caffeine did not significantly affect performance on all tests with the exception of the peripheral awareness (hand-eye coordination) test on which performance was higher after ingesting caffeine. The placebo treatment produced no effect on state anxiety, which contrasted with a significant rise in anxiety after caffeine consumption. State anxiety values were significantly greater after caffeine treatment relative to the placebo at pretest, and this difference persisted at posttest. These results demonstrated that the dose of caffeine increased scores on state anxiety for individuals who consumed less than three caffeinated beverages weekly but had very little effect on performance of low intensity tasks, except for a hand-eye coordination test involving peripheral awareness. Perhaps longer continuous performance of more demanding tasks would be more sensitive.     

Caffeine deprivation state modulates expression of acquired liking for caffeine-paired flavours

Previous studies found that caffeine consumers acquired a liking for the flavour of novel caffeinated drinks when these drinks were consumed repeatedly in a caffeine-deprived, but not nondeprived, state. Expression of this acquired liking appeared acutely sensitive to current caffeine deprivation state, but the use of between-subjects designs confounded interpretation of those studies. The present study evaluated these findings further using a within-subject design, with one flavour paired with caffeine (CS + ) and the second with the absence of caffeine (CS–). During four CS + and four CS– training days, 32 moderate caffeine consumers alternatively consumed a novel flavoured drink a CS + paired with caffeine and a CS– flavour paired with placebo. Participants evaluated both drinks before and after training in two motivational states: caffeine deprived and nondeprived. As predicted, pleasantness ratings for the caffeine-paired flavour increased overall. However, this acquired liking was only significant when tested in a caffeine-deprived state. These data are consistent with a conditioned-flavour preference model and imply that expression of acquired liking for a novel caffeinated flavour depends on the need for the effects of caffeine at the time when the drink is evaluated.     

Caffeine deprivation state modulates expression of acquired liking for caffeine-paired flavours

Previous studies found that caffeine consumers acquired a liking for the flavour of novel caffeinated drinks when these drinks were consumed repeatedly in a caffeine-deprived, but not nondeprived, state. Expression of this acquired liking appeared acutely sensitive to current caffeine deprivation state, but the use of between-subjects designs confounded interpretation of those studies. The present study evaluated these findings further using a within-subject design, with one flavour paired with caffeine (CS + ) and the second with the absence of caffeine (CS-). During four CS + and four CS- training days, 32 moderate caffeine consumers alternatively consumed a novel flavoured drink a CS + paired with caffeine and a CS- flavour paired with placebo. Participants evaluated both drinks before and after training in two motivational states: caffeine deprived and nondeprived. As predicted, pleasantness ratings for the caffeine-paired flavour increased overall. However, this acquired liking was only significant when tested in a caffeine-deprived state. These data are consistent with a conditioned-flavour preference model and imply that expression of acquired liking for a novel caffeinated flavour depends on the need for the effects of caffeine at the time when the drink is evaluated.     

The effect of caffeine on handwriting movements in skilled writers

In laboratory tasks, caffeine has been shown to improve psychomotor performance. The aim of the present experiment was to assess the effects of caffeine on a skilled everyday life task in habitual caffeine consumers. The assessment of handwriting movements of 20 adults was performed following the administration of 0mg/kg (placebo), 1.5mg/kg, 3.0mg/kg or 4.5mg/kg of caffeine. A digitising tablet was used for the assessment of fine motor movements. Participants were asked to perform a simple writing task. Kinematic analysis of handwriting movements showed that, in comparison to placebo administration, high doses of caffeine (i.e., 4.5mg/kg) can produce improvements in handwriting as indicated by more fluent handwriting movements as well as an increase in maximum velocity and maximum positive and negative accelerations. The results suggest that higher doses of caffeine can enhance psychomotor performance.     

ALPHABET LETTERS AS TOKENS: TRAINING PRESCHOOL CHILDREN IN LETTER RECOGNITION AND LABELLING DURING A TOKEN EXCHANGE PERIOD1

In token economies, we typically consider the instructional opportunities available during the periods of token delivery, but may overlook educational opportunities available at the time of token exchange. The present studies examined the use of labelled tokens and routines in the token exchange period to teach alphabet letter recognition to economically disadvantaged preschool children. The children earned points for a variety of academic behaviors in an early morning classroom setting. At no time were alphabet letters introduced or taught during class. Later, during a midmorning token exchange period, operated according to a department store model, the children were given their points in the form of poker chips inscribed with upper-case alphabet letters. They were required to discriminate among these lettered chips before exchanging them for backup reinforcers sold in four or five stores. To assess alphabet letter knowledge, probe evaluations were periodically conducted in which questions requiring alphabet letter recognition and labelling were asked. The answers to these questions were not reinforced. Alphabet letter training during token exchange periods consisted of having a child display the lettered chips, whereupon a teacher asked a number of recognition-type questions. Wrong answers were corrected, and correct answers praised. The child was allowed to exchange the tokens when the number required for a purchase had been recognized correctly. The periodic probe evaluations revealed consistent increases in correct alphabet letter recognition and, as a byproduct, alphabet labelling was facilitated, even though not explicitly trained. Thus, once the letters were recognized, correct labelling shortly followed. The sequential training of new sets of letters was used to demonstrate experimental control within subjects for two children. A control for exposure to the letters was provided by using the labelled tokens, but requiring the counting of chips rather than letter discrimination in the exchange period for two other children. This procedure produced chance levels of letter recognition, which were subsequently improved when the discrimination procedure was added. Posttraining probes, conducted at one and three weeks after training when the labelled tokens and discrimination routines were no longer in use, revealed the same high levels of recognition and labelling performance found during training. Thus, it appears that labelled tokens may be used to teach discriminations during token exchange periods so long as responses are differentiated on the basis of relevant dimensions of the stimuli.     

Aging, practice, and perceptual tasks: a diffusion model analysis

Practice effects were examined in a masked letter discrimination task and a masked brightness discrimination task for college-age and 60- to 75-year-old subjects. The diffusion model (Ratcliff, 1978) was fit to the response time and accuracy data and used to extract estimates of components of processing from the data. Relative to young subjects, the older subjects began the experiments with slower and less accurate performance; however, across sessions their accuracy improved because the quality of the information on which their decisions were based improved, and this, along with reduced decision criteria, led to shorter response times. For the brightness, but not the letter, discrimination task, the older subjects' performance matched that of the younger group by the end of 4 sessions, except that their nondecision components of processing were slightly slower. These analyses illustrate how a well-specified model can provide a unified view of multiple aspects of data that are often interpreted separately.