Obese and overweight individuals are less sensitive to information about meal times in portion-size judgements.

BACKGROUND: Obesity is related to a tendency to discount the future. Information regarding inter-meal interval (IMI) allows meal planning. We sought to assess how obese, overweight and lean people select portion sizes based on the length of an IMI. We hypothesised that individuals with a high body mass index (BMI) would discount information about the IMI. In addition, we investigated how reduced sensitivity to IMIs relates to monetary temporal discounting. METHODS: Participants (lean, n=35; overweight, n=31; obese, n=22) selected lunchtime portion sizes in response to information about the timings of their next meal. In seven trials, the time of the IMI was systematically manipulated, ranging from 'right now' to '8 h'. Participants then completed a monetary temporal discounting task. BMI was included as a continuous measure. For each participant, we conducted a linear regression of portion size on IMI to yield a gradient that reflected reduced sensitivity to future meal timings. RESULTS: As expected, participants selected larger portion sizes in response to a long IMI. Consistent with our hypothesis, individuals with a high BMI discounted information about the IMI (ß=-3.49, P=0.015; confidence interval (CI) 6.29 to -0.70). Monetary discounting also negatively predicted BMI (ß=-8.1, P=0.003; CI=-13.43 to -2.77), but did not correlate with IMI sensitivity (P>0.05). CONCLUSIONS: These results are the first to demonstrate that temporal discounting operates in planning from one meal to the next, and is more prevalent in obese and overweight, relative to lean individuals. Participants with a high BMI discounted concerns about potential future fullness and hunger in the IMI. Our observations might begin to explain associations between obesity and irregular meal timings or help to form the basis for a targeted intervention that promotes future thinking in meal planning.

Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies.

By reducing energy density, low-energy sweeteners (LES) might be expected to reduce energy intake (EI) and body weight (BW). To assess the totality of the evidence testing the null hypothesis that LES exposure (versus sugars or unsweetened alternatives) has no effect on EI or BW, we conducted a systematic review of relevant studies in animals and humans consuming LES with ad libitum access to food energy. In 62 of 90 animal studies exposure to LES did not affect or decreased BW. Of 28 reporting increased BW, 19 compared LES with glucose exposure using a specific 'learning' paradigm. Twelve prospective cohort studies in humans reported inconsistent associations between LES use and body mass index (-0.002 kg m(-)(2) per year, 95% confidence interval (CI) -0.009 to 0.005). Meta-analysis of short-term randomized controlled trials (129 comparisons) showed reduced total EI for LES versus sugar-sweetened food or beverage consumption before an ad libitum meal (-94 kcal, 95% CI -122 to -66), with no difference versus water (-2 kcal, 95% CI -30 to 26). This was consistent with EI results from sustained intervention randomized controlled trials (10 comparisons). Meta-analysis of sustained intervention randomized controlled trials (4 weeks to 40 months) showed that consumption of LES versus sugar led to relatively reduced BW (nine comparisons; -1.35 kg, 95% CI -2.28 to -0.42), and a similar relative reduction in BW versus water (three comparisons; -1.24 kg, 95% CI -2.22 to -0.26). Most animal studies did not mimic LES consumption by humans, and reverse causation may influence the results of prospective cohort studies. The preponderance of evidence from all human randomized controlled trials indicates that LES do not increase EI or BW, whether compared with caloric or non-caloric (for example, water) control conditions. Overall, the balance of evidence indicates that use of LES in place of sugar, in children and adults, leads to reduced EI and BW, and possibly also when compared with water.

Chronic treatment with a tryptophan-rich protein hydrolysate improves emotional processing, mental energy levels and reaction time in middle-aged women.

Common pharmacological treatments of mood disorders aim to modulate serotonergic neurotransmission and enhance serotonin levels in the brain. Brain serotonin levels are dependent on the availability of its food-derived precursor essential amino acid tryptophan (Trp). We tested the hypothesis that delivery of Trp via food may serve as an alternative treatment, and examined the effects of a Trp-rich, bioavailable dietary supplement from egg protein hydrolysate on cognitive and emotional functions, mood state, and sleep quality. In a randomised, placebo-controlled, parallel trial, fifty-nine mentally and physically healthy women aged 45-65 years received placebo (n 30) or the supplement (n 29) (both as 0.5 g twice per d) for 19 d. Emotional processing was significantly changed by supplementation, exhibiting a shift in bias away from negative stimuli. The results for the Affective Go/No-Go Task exhibited a slowing of responses to negative words, suggesting reduced attention to negative emotional stimuli. The results for the Facial Emotional Expression Rating Task also supported a shift away from attention to negative emotions and a bias towards happiness. An increase in arousal-like symptoms, labelled 'high energy', shorter reaction times and a slight benefit to sustained attention were observed in the treated subjects. Finally, when the supplement was taken 60-90 min before bedtime, a feeling of happiness before going to bed was consistently reported. In summary, daily consumption of a low-dose supplement containing bioavailable Trp may have beneficial effects on emotional and cognitive functions.

Lack of association between DRD2 and OPRM1 genotypes and adiposity.

BACKGROUND: Dopaminergic and opioid systems are both involved in food intake and appetite control. The dopamine D2 receptor gene (DRD2) and the µ-opioid receptor gene (OPRM1) therefore represent plausible candidates for association with obesity. OBJECTIVE: Previous studies of these variants have yielded inconsistent findings, which are likely due to insufficient statistical power. The aim of the current study was to determine whether, in a large population-based sample, there are associations between adiposity and (i) the A1 (T) allele of the Taq1A polymorphism (rs1800497) in DRD2 and (ii) the G allele of the A118G polymorphism (rs1799971) in OPRM1. STUDY POPULATION: Annual clinic-based measures of body mass index (BMI) and waist circumference were taken from children (N=3720) at 5 measurement time points from ages 7 through to 11 years. BMI was also recorded in their mothers (N=2460) at comparable time points and at pre-pregnancy. All participants were genotyped. Our study was powered (at 80%) to detect per-allele effects on BMI of 0.21 kg m(-2). RESULTS: Our results indicate a lack of association between DRD2 and OPRM1 genotypes and adiposity. Combining the data across mothers and children found per-allele effects on BMI of 0.02 kg m(-2) (95% confidence interval (CI): -0.17, 0.20), P=0.9 for rs1800497 and -0.08 kg m(-2) (95% CI: -0.29, 0.22), P=0.4 for rs1799971. As a positive control, we also examined the effect of FTO genotype over the same time period and confirmed the expected relationship between variability at this locus and higher adiposity. CONCLUSION: Our findings question existing evidence suggesting associations at DRD2 and OPRM1 loci and adiposity. They also highlight the caution required when employing candidate gene approaches to further our understanding of the neurobiology of eating and obesity.

No appetite efficacy of a commercial structured lipid emulsion in minimally processed drinks.

BACKGROUND/OBJECTIVES: Fabuless (Olibra) is a commercially structured lipid emulsion, claimed to be a food ingredient that is effective for food intake and appetite reduction. The present study assessed its efficacy in a yoghurt-based mini-drink undergoing low or minimal food manufacturing (thermal and shear) processes. SUBJECTS/METHODS: Study 1: Twenty-four healthy volunteers (16 female, 8 male; age: 18-47 years; body mass index (BMI): 17-28 kg m(-2)) took part in a randomised, placebo-controlled, double-blind parallel crossover trial. Consumption of a minimally processed 'preload' mini-drink (containing two different doses of Fabuless or a control fat) at 2 h after breakfast was followed by appetite and mood ratings, and food intake measured in ad libitum meals at 3 and 7 h post consumption of the preload. Study 2: As Study 1 (16 female, 8 male; age: 20-54 years; BMI: 21-30 kg m(-2)). A chilled, virtually unprocessed, preload breakfast mini-drink (containing minimally processed Fabuless or a control fat) was provided 5 min after a standardised breakfast, followed by appetite and mood ratings, and food intake measured in ad libitum meals at 4 and 8 h post consumption of the preload. RESULTS: The structured lipid emulsion tested had no significant effect on the primary measures of food intake or appetite. CONCLUSIONS: Even when exposed to minimal food-manufacturing conditions, Fabuless showed no efficacy on measures of appetite and food intake.

Supplementation with a low-moderate dose of n-3 long-chain PUFA has no short-term effect on bone resorption in human adults.

Previous research suggests that n-3 PUFA may play a role in bone health. The present analysis aimed to investigate the impact of n-3 PUFA supplementation on bone resorption in adult men and women. Serum samples from 113 mild-moderately depressed individuals (twenty-six males and eighty-seven females, aged 18-67 years) randomised to receive 1·48 g EPA+DHA/d (n 53) or placebo (n 60) for 12 weeks as part of a large recent randomised controlled trial were assayed for n-3 PUFA status and a bone resorption marker, C-terminal cross-linking telopeptide of type 1 collagen (ß-CTX). Regression analyses revealed that n-3 PUFA status following supplementation was associated with randomisation (placebo/n-3 PUFA) (B = 3·25, 95 % CI 2·60, 3·91, P < 0·01). However, ß-CTX status following supplementation was not associated with randomisation (B = - 0·01, 95 % CI - 0·03, 0·04). Change in ß-CTX status was also not associated with change in n-3 PUFA status (B = - 0·002, 95 % CI - 0·01, 0·01). These findings provide no evidence for an association between n-3 PUFA supplementation (1·48 g EPA+DHA/d) for 12 weeks and bone resorption in humans assessed by ß-CTX, and suggest that n-3 PUFA supplementation may be unlikely to be of benefit in preventing bone loss.

No clear evidence of an association between plasma concentrations of n-3 long-chain polyunsaturated fatty acids and depressed mood in a non-clinical population.

Previous research suggests that low n-3 long-chain polyunsaturated fatty acid (n-3PUFA) status is associated with higher levels of depression in clinical populations. This analysis aimed to investigate the relationship between depressed mood and n-3PUFA status in a non-clinical population. The analysis was conducted on data collected as part of a large randomized controlled trial investigating the impact of n-3PUFA supplementation on depressed mood in a community-based population. On entry into the trial, data on depressed mood were collected using the Depression, Anxiety and Stress Scales (DASS) and the Beck Depression Inventory (BDI). Plasma concentrations of various n-3PUFAs and n-6 long-chain polyunsaturated fatty acids (n-6PUFAs) were obtained from fasting venous blood samples, and various demographics were also measured. Using regression, there was no evidence of an association between either measure of depressed mood and any of the measures of n-3PUFA status or of n-6PUFA:n-3PUFA ratios. Clear associations were also not found when demographic factors were included in the analyses. These findings suggest that n-3PUFAs may not have a role in the aetiology of minor depression. This is also consistent with the results of other studies that have not demonstrated an association between depressed mood and n-3PUFA status in non-clinical populations and epidemiological studies that have not demonstrated an association between depressed mood and n-3PUFA intake in these populations.

Is there a role for n-3 long-chain polyunsaturated fatty acids in the regulation of mood and behaviour? A review of the evidence to date from epidemiological studies, clinical studies and intervention trials.

Selected biochemical evidence suggests a potential role for n-3 long-chain PUFA (n-3PUFA) in the regulation of mood and behaviour. The present paper reviews the relevant evidence, to date, from epidemiological studies, clinical studies and intervention trials. Most evidence is available investigating a role for n-3PUFA in depression, depressive illness and suicidal behaviour, but work is also available on anxiety and anxiety-related disorders, fatigue and fatigue-related disorders, aggression, hostility and anti-social behaviour, inattention, impulsivity and attention deficit hyperactivity disorder and schizophrenic disorders. For all these aspects of mood and behaviour, the evidence available is currently limited and highly inconsistent, both in terms of study methodology and study findings. There is a clear need for further work in this area.

Parental beliefs about portion size, not children's own beliefs, predict child BMI.

BACKGROUND: Increases in portion size are thought by many to promote obesity in children. However, this relationship remains unclear. Here, we explore the extent to which a child's BMI is predicted both by parental beliefs about their child's ideal and maximum portion size and/or by the child's own beliefs. METHODS: Parent-child (5-11 years) dyads (N = 217) were recruited from a randomized controlled trial (n = 69) and an interactive science centre (n = 148). For a range of main meals, parents estimated their child's 'ideal' and 'maximum tolerated' portions. Children completed the same tasks. RESULTS: An association was found between parents' beliefs about their child's ideal (ß = .34, p < .001) and maximum tolerated (ß = .30, p < .001) portions, and their child's BMI. By contrast, children's self-reported ideal (ß = .02, p = .718) and maximum tolerated (ß = -.09, p = .214) portions did not predict their BMI. With increasing child BMI, parents' estimations aligned more closely with their child's own selected portions. CONCLUSIONS: Our findings suggest that when a parent selects a smaller portion for their child than their child self-selects, then the child is less likely to be obese. Therefore, public health measures to prevent obesity might include instructions to parents on appropriate portions for young children.

The measurement of transmembrane electrical potential with lipophilic cations.

The binding of lipophilic cation probes of membrane potential to cells was re-examined. Even concentrations of probe molecules as low as 100 nM were found to reduce delta psi and thus many commonly used techniques for delta psi determination are inappropriate. Binding was found to be a linear function of probe concentration and independent of pH. The proportionality constant for binding has been equated to an "apparent binding volume' for [3H]TPP+ with units of microliter/mg dry weight of cells. This "apparent binding volume' is thermodynamically equivalent to the volume of cell membrane multiplied by the partition coefficient of [3H]TPP+ for cell membrane and was equivalent to 9.10 +/- 0.33 microliters/mg dry weight in Enterococcus faecalis. It was concluded that the most accurate method for delta psi determination was to use nanomolar concentrations of lipophilic cations and appropriate correction for energy dependent binding.

Exercise-induced increases in atrial natriuretic factor are attenuated by endurance training.

Short-term exercise has been associated with increased plasma levels of atrial natriuretic factor, a potent dilating and natriuretic hormone. In this study, the effect of exercise training on atrial natriuretic factor release during short-term exercise was investigated in men without a history of cardiovascular or other major disease. A well trained group of 10 men who exercised an average of 6,618 kcal/week was compared with a minimally trained group of 9 men who exercised 1,479 kcal/week. Maximal oxygen uptake was 55.2 ml/kg per min in the well trained group and 42.5 ml/kg per min in the minimally trained group (p less than 0.05). Plasma for atrial natriuretic factor, norepinephrine and epinephrine was obtained at rest, at 4 min of exercise and at maximal exercise. Atrial natriuretic factor was lower at rest in the minimally trained than in the well trained men (23 vs. 35.9 pg/ml, p less than 0.05). At maximal exercise, atrial natriuretic factor increased 2.6 times the value at rest in minimally trained men (59.8 pg/ml, p less than 0.05 vs. rest), but did not change in well trained men (34 pg/ml). In minimally trained men at rest, at 4 min of exercise and at maximal exercise, plasma levels of atrial natriuretic factor correlated with heart rate, cardiac output, mean arterial pressure and plasma levels of norepinephrine and epinephrine; these correlations were not found in the well trained group. Thus, short-term exercise results in a significant increase in atrial natriuretic factor in minimally trained but not in well trained men.(ABSTRACT TRUNCATED AT 250 WORDS)

Assessment of myocardial perfusion by videodensitometry in the canine model.

Assessment of the functional severity of coronary stenoses has become increasingly important as the intrinsic limitations of coronary angiography have been documented. Videodensitometric coronary flow reserve has been proposed as a means to assess the physiologic significance of a coronary stenosis in humans. This study compared videodensitometric assessment of coronary flow with microsphere quantitation in the closed chest canine model. In five dogs, flow rates were assessed at baseline, after vasodilation with adenosine, after vasoconstriction with vasopressin and during rapid cardiac pacing. The videodensitometric peak density, time to one-half peak density and washout time (time from peak to one-half peak density) were compared at each flow state with flow assessed by microsphere injection. Reproducibility of videodensitometric measurements from two different coronary injections during the same flow state was best with peak density (r = 0.94). Videodensitometric flow ratios (flow state under study to flow at rest) using peak density demonstrated a fair correlation with flow ratios by microsphere (r = 0.81). There was poor correlation between flow ratios when time to one-half peak or washout time was used. Videodensitometric flow measurements used in vivo to assess a wide range of drug-induced coronary flows may not accurately reflect coronary flow measured by microsphere.

Meal patterns and food selection during the development of obesity in rats fed a cafeteria diet.

Offering preferred foods in addition to laboratory chow led immediately to a marked increase in both mean meal size (MMS) and meal frequency (MF). As body weight increased over a 5 months period, MF declined to a low level but MMS remained high. Within a majority of meals there was substantial consumption of only one food item. Nonetheless, when "mixed" meals were eaten these were usually larger than "exclusive" meals. With more than one preferred food available there was a significant tendency to alternate consumption of food types from one meal to the next. This disappeared at inter-meal intervals longer than 90 minutes. With one preferred food available, only MMS (and not MF) was increased and the degree of hyperphagia and obesity were reduced. The findings suggest the following conclusions: Both palatability (preference value for a particular food) and variety (availability of different types of food) have incremental, but distinguishable, effects on food consumption and mean parameters. Palatability mainly influences meal size, whereas variety exerts an effect on meal size and inter-meal interval. However, the potential effect of variety on overall intake is probably somewhat reduced by the tendency to eat only one type of food in each meal. Obesity has an inhibitory influence on feeding, operating primarily through a reduction in mean frequency.

Absence of hostility in outpatients after administration of halazepam--a new benzodiazepine.

A number of benzodiazepine have been shown to increase hostility and aggression. This study examines whether halazepam, a new benzodiazepine structurally very similar to diazepam, is associated with increases in hostility. Fifty-one adult outpatients in a double blind, 6 week study were randomly assigned either halazepam or placebo. Hostility was measured by changes in response on four different scales, the anger-hostility factor of the Patient Symptom Checklist and three MMPI hostility scales. The results of our study indicated that halazepam does not induce significant changes in hositility.

Mitochondrial metabolism following traumatic brain injury in rats.

Although a number of studies of traumatic brain injury have implicated mitochondrial dysfunction as a cause of altered posttraumatic energy metabolism, no studies to date have isolated mitochondria and measured their respiratory capacity following trauma. The present study sought to determine whether mitochondrial capacity for oxidative phosphorylation is adversely affected by fluid-percussion-induced traumatic brain injury in rats. Prior to brain injury, the mitochondrial respiratory control ratio was 4.3 +/- 0.2 and the ratio of nmoles of ADP phosphorylated per natom oxygen consumed (ADP/O ratio) was 2.66 +/- 0.09. After injury (2.8 atm; t = 4 h), there were slight but not significant alterations in ADP/O ratio (2.41 +/- 0.07) and state 3 respiratory rate (ADP stimulated); however, there were no changes in the respiratory control ratio. These data suggest that traumatic brain injury, unlike ischemia, does not cause uncoupling of ATP synthesis from respiration, and that brain mitochondria are quite resistant to trauma-induced injury.

Effect of anorexic drugs on food intake and the micro-structure of eating in human subjects.

Human volunteer subjects of normal weight received oral doses of (+)amphetamine (10 mg) or (+/-)fenfluramine (30 mg and 60 mg) together with a placebo control according to a within-subjects design. The effects of these treatments were monitored by measuring food intake in a test meal, subjective ratings of hunger motivation and the micro-structure of eating behaviour abstracted from videotaped recordings of the test meal. Various measures of the rate of feeding were computed from these recordings. Amphetamine and fenfluramine (60 mg) showed generally similar effects on food intake and on the subjective experience of hunger, but displayed differing actions on the fine structure of eating. Amphetamine increased latency to initiation of eating and increased the rate of food ingestion, whilst fenfluramine slowed the local rate of eating and eliminated the characteristic decline in the rate of feeding across the course of a meal. These findings display certain resemblance to the results of animal experiments involving similar pharmacological manipulations and emphasise the importance of measuring rate of feeding in animal and human studies. The results of this study suggest that the micro-analysis of feeding behaviour not only provides a tool for understanding systems involved in the modulation of food consumption but also reveals information which may be helpful for the use of drugs in the treatment of obesity.

Effects of low doses of caffeine on cognitive performance, mood and thirst in low and higher caffeine consumers.

RATIONALE: Caffeine is present in many widely consumed drinks and some foods. In the fairly extensive literature on the psychostimulant effects of caffeine, there are few dose-response studies and even fewer studies of the effects of doses of caffeine lower than 50 mg (the range of the amounts of caffeine contained in, for example, a typical serving of tea or cola). OBJECTIVE: This study measured the effects of 0, 12.5, 25, 50 and 100 mg caffeine on cognitive performance, mood and thirst in adults with low and moderate to high habitual caffeine intakes. METHODS: This was a double-blind, within-subjects study. Following overnight caffeine abstinence, participants (n=23) completed a test battery once before and three times after placebo or caffeine administration. The test battery consisted of two performance tests, a long duration simple reaction time task and a rapid visual information processing task, and a mood questionnaire (including also an item on thirst). RESULTS: Effects on performance and mood confirmed a psychostimulant action of caffeine. All doses of caffeine significantly affected cognitive performance, and the dose-response relationships for these effects were rather flat. The effects on performance were more marked in individuals with a higher level of habitual caffeine intake, whereas caffeine increased thirst only in low caffeine consumers. CONCLUSIONS: After overnight caffeine abstinence, caffeine can significantly affect cognitive performance, mood and thirst at doses within and even lower than the range of amounts of caffeine contained in a single serving of popular caffeine-containing drinks. Regular caffeine consumers appear to show substantial tolerance to the thirst-increasing but not to the performance and mood effects of caffeine.

Conditioned flavour preference negatively reinforced by caffeine in human volunteers.

This study examined whether 100 mg caffeine could reinforce preference for the flavour of a novel drink in moderate caffeine users, both after overnight caffeine abstinence and 2 h after receiving 100 mg caffeine, using a two-stage between-groups procedure with 36 volunteers. In the first stage, liking for a test drink (fruit tea) was assessed at breakfast following overnight caffeine abstinence, with half the subjects receiving caffeine. Liking for the tea increased significantly over four trials for subjects receiving caffeine, and decreased significantly in those without caffeine. These effects were greatest in subjects who rated the drink as highly novel. In stage two, subjects evaluated a second drink (fruit-juice) 2 h after receiving the tea, and again half the subjects received caffeine Those subjects who received caffeine in stage two but not stage one showed a significant increase in liking for the fruit-juice over the 4 test days, whereas subjects who did not receive caffeine at either stage showed a progressive decrease in liking for this drink. In contrast, no significant change in liking for the fruit-juice was seen at stage two for subjects who had received caffeine in stage one, regardless of the presence or absence of caffeine at stage two. Caffeine at breakfast increased ratings of energetic and lively, and energetic ratings also increased following caffeine in the fruit-juice in subjects who had not had caffeine at breakfast. Overall, these data are consistent with a negative reinforcement model of caffeine reinforcement, and demonstrate further the utility of the conditioned flavour preference method for evaluating reinforcing effects of drugs in humans.

The effects of food deprivation and incentive motivation on blood glucose levels and cognitive function.

The current study investigated the relationships between blood glucose levels, mild food deprivation, sympathetic arousal, and cognitive processing efficiency. Subjects (n = 82) were randomly assigned to four experimental conditions, comprising combined manipulations of food deprivation and incentive motivation. Baseline and mid-session measurements of blood glucose, blood pressure and pulse rate were taken. Subjects completed a number of measures of cognitive processing efficiency and self report measures of affective and somatic state. Although glucose levels were lowered following food deprivation, there was no significant detrimental effect of food deprivation on task performance. However, improved recognition memory processing times were associated with deprivation. Incentive motivation was associated with faster simple reaction times and higher diastolic blood pressure. There were no significant relationships between glucose levels and task performance, further supporting the hypothesis that the brain is relatively invulnerable to short food deprivation.

Overnight caffeine abstinence and negative reinforcement of preference for caffeine-containing drinks.

It has been suggested that liking for the taste, flavour and aroma of, for example, coffee and tea is acquired through the process of classical conditioning, involving association of these orosensory cues with the psychopharmacological consequences of caffeine ingestion. Accordingly, this study investigated caffeine reinforcement by assessing changes in preference for a novel drink consumed with or without caffeine. Particular care was taken to use "ecologically valid" procedures; that is, overnight caffeine abstinence followed by a cup-of-coffee equivalent dose of caffeine (70 mg) at breakfast. Caffeine had no significant effects on drink preference or mood in subjects with habitually low intakes of caffeine. In contrast, moderate users of caffeine developed a relative dislike for the drink lacking caffeine and showed somewhat lowered mood following overnight caffeine abstinence (e.g., less lively, clearheaded and cheerful), which was significantly improved by caffeine. These together with other recent results strongly suggest that, in everyday life, caffeine reinforcement can occur as the result of the alleviation by caffeine of the adverse effects of overnight caffeine abstinence (negative reinforcement). They also demonstrate the utility of this flavour-conditioning procedure, which could be applied in the wider investigation of the reinforcing properties of drugs.