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Biomedical subjects

H de Wit

Publications and source records attributed to H de Wit.

At least 73 records · Page 4Linked to original sources
PubMed1995

Caffeine withdrawal symptoms and self-administration following caffeine deprivation.

This study examined the effects of complete or partial caffeine deprivation on withdrawal symptomatology and self-administration of coffee in caffeine-dependent coffee drinkers. Nine habitual coffee drinkers abstained from dietary sources of caffeine for 33.5 h. Caffeine deprivation was manipulated by administering capsules containing 0%, 50%, or 100% of each subject's daily caffeine intake (complete, partial, and no deprivation conditions). Caffeine withdrawal symptomatology was measured using self-report questionnaires. Caffeine self-administration was measured using: i) the amount of coffee subjects earned on a series of concurrent random-ratio schedules that yielded coffee and money reinforcers; ii) the amount of earned coffee they consumed. Saliva samples revealed that subjects complied with the caffeine abstinence instructions. Caffeine withdrawal symptoms occurred reliably following complete caffeine deprivation, though not in the partial deprivation condition. Caffeine self-administration was not related to deprivation condition. We conclude that caffeine withdrawal symptomatology is not necessarily associated with increased caffeine consumption.

Adult↗
PubMed1995

Acute subjective responses to paroxetine in normal volunteers.

The purpose of this study was to compare the subjective effects of the selective serotonin reuptake inhibitor, paroxetine, to those of the prototypic stimulant, d-amphetamine. Ten healthy volunteers attended 5 sessions and received paroxetine (10, 20, 50 mg), d-amphetamine (20 mg), and placebo. Subjective effects were measured at regular intervals for 26-30 h. Paroxetine and d-amphetamine produced highly dissimilar effects on mood. For example, whereas d-amphetamine increased ratings of euphoria, drug high, and desire for drug, paroxetine produced no effects on these measures. Conversely, whereas paroxetine increased ratings of Confusion and Fatigue, d-amphetamine did not. These findings suggest that serotonin does not play a significant role in mediating the positive subjective effects of stimulant drugs.

Adult↗
PubMed1994

Interleukin-4 receptor regulation in human monocytic cells.

The regulation of the interleukin-4 receptor (IL-4R) was studied at mRNA and protein level in monocytic cells on stimulation with activators of different intracellular signaling pathways and IL-4. Activation of protein kinase C-dependent pathways with phorbol myristate acetate (PMA) or activation of protein kinase A-dependent pathways with DBcAMP and prostaglandin E2 resulted in an augmented IL-4R expression at mRNA and protein level. Transcriptional and posttranscriptional mechanisms seemed to be involved in the promotive effect of DBcAMP because the transcription rate increased 1.8-fold, and the half-life of IL-4R mRNA was prolonged to 150 minutes compared with 120 minutes in unstimulated cells. In contrast, the effect of PMA could only be ascribed to changes at transcriptional level. However, activation of Ca(2+)-dependent pathways with A23187 or stimulation with IL-4 had no effect on the IL-4R expression. The unresponsiveness to IL-4 could not be ascribed to a nonfunctional receptor because IL-4 did modulate the CD14, CD23, and HLA-DR antigen expression. These results are in contrast with IL-4R regulation in T cells, which is affected by IL-4- and Ca(2+)-dependent pathways. The discrepancy might be caused by the presence of the common IL-2 receptor gamma chain (gamma c) in T cells and the absence of the gamma c in monocytic cells, as has been shown by polymerase chain reaction. These data indicate that IL-4Rs are differentially regulated, depending on the cell type studied.

Base Sequence↗
PubMed1994

Preference for ethanol and diazepam in light and moderate social drinkers: a within-subjects study.

Preference for ethanol (versus placebo) and diazepam (versus placebo) was assessed in light and moderate social drinkers. The study was designed to investigate the relationship of habitual alcohol use to the subjective and behavioral effects of the two drugs. A secondary purpose of the study was to investigate relationships within subjects in their responses to ethanol and diazepam. Light drinkers (n = 13) who consumed one to five drinks per week and moderate drinkers (n = 14) who consumed seven or more drinks per week participated in two seven-session choice experiments, one assessing preference for 0.5 g/kg ethanol versus placebo and the other assessing preference for 20 mg diazepam versus placebo. Drugs were administered double-blind and double-dummy, and the order of participation in the two experiments was counterbalanced. Sessions were conducted during the evenings in a comfortable laboratory environment. The primary dependent measure was the number of times each subject chose the drug (i.e., ethanol or diazepam) over placebo. Subjective and objective measures of the drugs' effects were obtained using standardized self-report questionnaires and psychomotor tests. Whereas both groups preferred the ethanol over placebo (i.e., 63% and 83% ethanol choice for light and moderate drinkers, respectively), only the moderate drinkers preferred the diazepam over placebo (i.e., 40% and 73% diazepam choice for light and moderate drinkers, respectively). Subjective responses to the drugs were generally similar across the groups, although on some measures the light drinkers reported more marked drug effects. The number of times each subject chose ethanol was positively correlated with the number of times he or she chose diazepam (r = 0.57), and on subjective measures, responses to ethanol and diazepam were positively correlated. Thus, subjective and behavioral responses to diazepam and ethanol were related to habitual alcohol consumption, and most notably, moderate drinkers were more likely than light drinkers to prefer diazepam over a placebo.

Adult↗
PubMed1994

Relationship between subjective effects and drug preferences: ethanol and diazepam.

The relationship between subjective effects and drug preferences in normal volunteers was explored in a meta-analysis of several previously published studies. Subjective effects of, and preference for, ethanol and diazepam vs. placebo were measured using a choice procedure. Subjects were grouped according to their drug choices: 'non-choosers' never chose drug, whereas 'choosers' always chose drug. The two groups were compared on their subjective responses to drug and on demographic variables. Ethanol decreased Arousal, Elation, Positive Mood and Vigor, and increased Anxiety, Depression and Fatigue in the non-choosers, whereas it increased Arousal and Vigor in the choosers. Ethanol choosers were also more likely to be males and/or full-time students than non-choosers. Diazepam produced sedative-like effects in both choosers and non-choosers, but markedly decreased Anxiety and increased Friendliness in choosers only. Diazepam choice was also associated with more frequent recreational use of marijuana and stimulants. Thus, both demographic variables and subjective drug effects were related to drug preference.

Adult↗
PubMed1994

Differential regulation of M-CSF and IL-6 gene expression in monocytic cells.

Using the human monocytic cell line Mono Mac 6 we studied the involvement of Ca2+, protein kinase A (PKA), and protein kinase C (PKC) dependent pathways in the regulation of M-CSF and IL-6 gene expression. The results demonstrate that on activation with the calcium ionophore A23187 both M-CSF and IL-6 mRNA are induced after 3 and 6 h respectively. Co-stimulation with A23187 plus PMA resulted in an up-regulation of M-CSF mRNA and a down-regulation of IL-6 mRNA. Conversely co-stimulation with A23187 plus DBcAMP resulted in a down-regulation of M-CSF mRNA and an up-regulation of IL-6 mRNA. Nuclear run-on and mRNA half-life studies showed that the effects on the M-CSF expression were related to changes at transcriptional and post-transcriptional level. In contrast, the effects on the IL-6 gene expression seems to be mediated at post-transcriptional level. With regard to the secretion of the IL-6 protein it was shown that it closely follows the accumulation of IL-6 mRNA. Taken together, the data show that several intracellular signalling pathways control strictly the cytokine expression in monocytic cells which gives the cells the opportunity to respond variably to external activation signals.

Bucladesine↗
PubMed1994

Personality and drug preferences in normal volunteers.

This study examined the relationship between drug preferences as measured in a laboratory-based choice procedure and measures of personality and attitudes toward drugs. Healthy volunteers participated in laboratory-based double-blind studies measuring preference for ethanol or diazepam vs placebo. Frequency of drug choice was examined in relation to subjects' scores on personality questionnaires. Drug choice was not related to any of the personality measures examined. Personality scores were, however, related to both gender and habitual drug use. These data suggest that personality does not strongly influence responses to single doses of drugs as assessed under controlled conditions. Personality may, nevertheless, affect drug use in natural settings via other mechanisms (e.g., interacting with psychosocial variables).

Adult↗
PubMed1993

Subjective and behavioral effects of diazepam depend on its rate of onset.

This study addressed the assumption that rate of onset affects the euphorigenic effects of drugs. Drugs with rapid onset are commonly thought to be more euphorigenic than drugs with slower onset, but this idea has rarely been studied directly. Nine healthy male social drinkers, with no history of drug- or alcohol-related problems, participated in three sessions. On each session they received oral doses of placebo (PLAC), diazepam in a rapid onset condition (FAST), or diazepam in a slow onset condition (SLOW). In the FAST condition, they received a single 20 mg dose, whereas in the SLOW condition they received six 4 mg doses administered at 30-min intervals. Plasma levels of diazepam and desmethyldiazepam, subjective effects (including measures of euphoria), psychomotor performance and vital signs were monitored throughout each session. Although the FAST and SLOW conditions led to similar peak plasma levels of drug, the peak was attained earlier in the FAST condition (61 min versus 220 min). Subjects' scores on a measure of euphoria (MBG scale of the ARCI) were significantly higher in the FAST condition compared to the SLOW and PLAC conditions. Subjects exhibited significantly more behavioral signs of intoxication and greater psychomotor impairment in the FAST condition. Sedative effects of the drug were similar in magnitude, but the effects lasted slightly longer in the FAST condition. On several measures diazepam produced similar effects in the two conditions (e.g., ratings of strength of drug effect). These data provide limited support for the notion that a faster rate of onset of drug effects is associated with greater euphoria.

Adult↗
PubMed1993

Reinforcing effects of extended inhalation of nitrous oxide in humans.

The subjective, psychomotor and reinforcing effects of nitrous oxide at subanesthetic doses (30% and 40% in oxygen) were determined in normal healthy volunteers using a choice paradigm. Thirty percent nitrous oxide was chosen no more often than oxygen (41.6% choice rate), indicating that, for most of the subjects tested, extended inhalation of this nitrous oxide concentration was no more reinforcing than oxygen inhalation. Forty percent nitrous oxide was chosen significantly less often than oxygen (22% choice rate), indicating that, for most of the subjects tested, extended inhalation of this nitrous oxide concentration was less reinforcing than oxygen. Nitrous oxide produced robust subjective effects (e.g., increased ratings of 'high,' 'tingling,' and 'dizzy'). Subjects who chose nitrous oxide reported pleasant subjective effects and liked it, while those who chose placebo reported unpleasant subjective effects and disliked it. Both concentrations of nitrous oxide impaired psychomotor performance in all subjects. The lack of reinforcing effects noted in the present study, given nitrous oxide's known abuse potential, is discussed.

Administration, Inhalation↗
PubMed1993

Interferon-gamma enhances the LPS-induced G-CSF gene expression in human adherent monocytes, which is regulated at transcriptional and posttranscriptional levels.

Human adherent monocytes were studied with regard to the expression of granulocyte colony-stimulating factor (G-CSF) at mRNA and protein levels in response to lipopolysaccharide (LPS) and gamma-interferon (IFN-gamma) stimulation. Monocytes did not express G-CSF transcripts in response to IFN-gamma treatment. In contrast, monocytes exposed to IFN-gamma plus LPS showed a dose-dependent increase in G-CSF mRNA accumulation and protein secretion compared to LPS-stimulated monocytes. The augmented G-CSF mRNA expression in response to IFN-gamma plus LPS was the result of a slight increase in the G-CSF transcription rate (2.2-fold) and a more than 6-fold increase in the G-CSF mRNA half-life (20 minutes vs. > 120 minutes). In addition, it was shown that the effects of IFN-gamma on LPS-induced G-CSF protein secretion could be mimicked by the calcium ionophore A23187, suggesting that the Ca(2+)-dependent pathway might be triggered after binding of the ligand to the receptor. Finally, it was observed that the potentiating effects of IFN-gamma on LPS-induced G-CSF secretion could be blocked by interleukin-4 (IL-4). These data indicate that two cytokines produced by activated T cells have opposite effects on G-CSF production by human activated monocytes.

Blotting, Northern↗
PubMed1992

Subjective and behavioral responses to intravenous fentanyl in healthy volunteers.

Fentanyl is a mu opiate agonist which is occasionally abused by medical personnel who have ready access to the drug. We examined in healthy volunteers (N = 13) the subjective and psychomotor-impairing effects of intravenous fentanyl (0-100 micrograms/70 kg). A randomized, placebo-controlled, crossover design was used in which subjects were injected with 0, 25 (N = 6), 50 and 100 micrograms/70 kg fentanyl in a double-blind fashion. Subjects completed several questionnaires commonly used in abuse liability testing studies before drug injection and at periodic intervals for up to 3 h after drug injection. Subjects also completed several psychomotor tests at these times. Some aspects of psychomotor functioning (e.g., eye-hand coordination) were impaired by fentanyl. Fentanyl produced dose-related increases in ratings of "high" and "sedated," but also tended to produce dysphoria and somatic symptomatology. Most subjects reported liking the effects of the two higher doses of fentanyl for at least a brief time after injection, but they varied widely in their linking ratings across the 3-h post-drug injection period. Despite the transient increases in liking ratings, fentanyl did not increase scores on a widely-used measure of drug-induced euphoria (morphine-benzedrine group scale of the Addiction Research Center Inventory). The present results suggest that some medical personnel who experiment with fentanyl may like it, and thus be at increased risk for abusing the drug in the future.

Adult↗
PubMed1992

Rate of increase of plasma drug level influences subjective response in humans.

This study addressed the commonly held, but seldom tested, notion that faster rates of increase of drug effects are associated with more positive subjective effects. Sodium pentobarbital was administered to normal healthy volunteers in either a single oral dose or in a series of divided, cumulating doses, and subjective responses were monitored. Twelve subjects participated in three weekly sessions, during which they received capsules containing placebo, 150 mg pentobarbital in a single dose (SIN) or 180 mg pentobarbital administered in six divided doses (DIV) of 30 mg every 30 min. Doses of pentobarbital in the SIN and DIV were selected to produce similar peak plasma levels. Blood samples were obtained at regular intervals for plasma drug level determinations, and throughout the session subjects completed self-report mood questionnaires (e.g., Profile of Mood States, visual analog ratings of drug liking and drug "high") and psychomotor performance tests (e.g., Digit Symbol Substitution Test). As expected, the SIN and DIV conditions yielded similar peak levels of pentobarbital, but the peak was attained more rapidly in the SIN condition. Despite the similarity in peak plasma levels, subjects reached greater peaks in ratings of "high" and wanted more of the drug when they were in the SIN condition. On an end-of-session liking questionnaire they also reported significantly greater liking of the drug in the SIN condition. On other measures of drug effects (e.g., sedation and psychomotor impairment) no significant differences were observed between the conditions. Thus, the rate of increase of the drug's effects specifically influenced subjects' ratings on subjective measures (e.g., "high" and liking) that may be associated with risk for abuse.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Lack of effect of social context on the reinforcing effects of diazepam in humans.

The reinforcing effects of diazepam (DZP) were compared under two conditions in human volunteers using a cumulative dose procedure. Under the social (SOC) condition, groups of two to four subjects participated concurrently whereas in the solitary (SOL) condition subjects participated individually. During the first four sessions of each condition, subjects received 20 mg DZP in five divided doses (4 mg) in two of the sessions and placebo (PL) in the other two sessions. Each drug (DZP or PL) was administered in a distinctively colored capsule and labeled by letter code. During the last three choice sessions, subjects chose which capsule they wished to self-administer and were allowed to choose up to a maximum of seven capsules (28 mg DZP) during each session. Subjects also filled out questionnaires that assessed momentary mood. Overall, DZP was chosen on 33% of choice sessions and there were no differences across conditions. There was a tendency for choice to be correlated with levels of weekly alcohol consumption and liking scores, and as well the latter two measures were correlated. DZP produced sedative-like subjective effects that did not appear to be related to setting, choice of drug in the study, or alcohol drinking history. These results partially confirm previous reports of a relationship between DZP preference and alcohol consumption, but differ from previously reported studies in the overall lower level of DZP choice.

Adult↗
PubMed1992

Self-administration of pentobarbital in light and moderate alcohol drinkers.

Preference for a moderate dose of pentobarbital was assessed in light and moderate alcohol drinkers using a double-blind, placebo-controlled laboratory choice procedure. Sixteen light drinkers (less than six alcoholic drinks per week) and 13 moderate drinkers (six or more drinks per week) participated in a seven-session study in which they first sampled capsules containing pentobarbital (150 mg) or placebo and then chose and ingested the capsule they preferred. Subjective and behavioral measures were obtained at regular intervals during each session to characterize the drug's effects. Both groups chose pentobarbital less often than placebo: Mean pentobarbital choice in light drinkers was 20.8% and in moderate drinkers was 38.5%. Pentobarbital choice and drug liking ratings were highest among male moderate drinkers but still did not exceed placebo levels. The drug did not increase scores on standardized measures of drug euphoria, even among the most frequent choosers or the heaviest alcohol consumers. The results extend previous reports showing that individuals without histories of drug abuse, even those who are moderate consumers of alcohol, do not self-administer sedative/anxiolytic drugs or experience their effects as euphorigenic.

Adult↗
PubMed1992

The effects of a restricted feeding regimen on cigarette smoking in humans.

The effects of 3 days of restricted feeding (800 kcal/day) on cigarette consumption, smoke exposure, and mood were studied in five male research volunteers. A within-subjects design was used in which subjects were exposed in an inpatient research unit to either a nutritionally-balanced diet containing 800 kcal (RESTRICTED DIET) or 3,000 kcal (NORMAL DIET) per day for 3 consecutive days. At least 2 weeks separated diet conditions. Dependent measures included number of cigarettes smoked per day in each diet condition, biological exposure levels (carbon monoxide and plasma cotinine levels), and mood. Number of cigarettes smoked per day did not differ significantly across diet conditions. Biological exposure to carbon monoxide and to cotinine, a metabolite of nicotine indicative of chronic nicotine exposure, also did not differ significantly between conditions. Fatigue scores from the Profile of Mood States were significantly elevated in the RESTRICTED DIET condition. Not surprisingly, subjects in this condition also reported feeling more hungry throughout the day than in the NORMAL DIET condition. From our study results, we conclude that a short period of "dieting," and the resulting hunger elicited from such a diet, do not increase cigarette consumption or smoke exposure in humans.

Adult↗
PubMed1992

Effects of setting on the subjective and behavioral effects of d-amphetamine in humans.

The effects of setting on the subjective and behavioral effects of 20 mg oral d-amphetamine were studied in eight healthy volunteers. A within-subjects design was used in which subjects ingested either amphetamine or placebo capsules in either an inpatient (isolated laboratory room) or an outpatient (normal daily environment) setting. The order of the four experimental conditions was randomized across subjects. Subjective drug effects were assessed using the Profile of Mood States, the Addiction Research Center Inventory, a Visual Analogue Scale, and a Drug Effects/Liking questionnaire, completed prior to and 1, 3, and 6 h after capsule ingestion. In addition, an End-of-Session questionnaire measuring overall drug liking and drug identification was completed at the 6-h timepoint. Subjects wore wrist monitors to record their physical activity levels during the 6-h postingestion period. Amphetamine produced typical stimulant-like subjective effects such as elation, euphoria, and friendliness, but the setting neither quantitatively nor qualitatively altered the drug response.

Adult↗
PubMed1992

Effects of fasting on responses to intravenous fentanyl in healthy volunteers.

The effects of food deprivation on the subjective, psychomotor, and physiological responses to intravenous fentanyl (50 micrograms/70 kg) were studied in 6 healthy male volunteers. A randomized, placebo-controlled, crossover design was used in which subjects were injected with fentanyl or saline after either 2, 12, or 24 hours of fasting. Subjects completed several subjective effects questionnaires as well as psychomotor tasks prior to, and at regular intervals, following the intravenous injection for a 3-hour period. An observer-rated behavioral checklist was completed at regular intervals during the session and several physiological measures (including measurement of pupil size) were recorded. Fentanyl induced opiate-like mood changes, miosis (pupil constriction), and impairment of extraocular muscle control, and 4 of the 6 subjects reported liking the effects; however, fasting had no impact on any of fentanyl's effects. We conclude that food deprivation up to 24 hours does not alter the subjective, psychomotor, or physiological response to the opiate, fentanyl.

Adult↗